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PMID: 21363960 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications.

Genes & development ·Vol. 25 ·No. 5 ·2011-03-01 ·Pages 409-33

Polo SE, Jackson SP

Abstract

Genome integrity is constantly monitored by sophisticated cellular networks, collectively termed the DNA damage response (DDR). A common feature of DDR proteins is their mobilization in response to genotoxic stress. Here, we outline how the development of various complementary methodologies has provided valuable insights into the spatiotemporal dynamics of DDR protein assembly/disassembly at sites of DNA strand breaks in eukaryotic cells. Considerable advances have also been made in understanding the underlying molecular mechanisms for these events, with post-translational modifications of DDR factors being shown to play prominent roles in controlling the formation of foci in response to DNA-damaging agents. We review these regulatory mechanisms and discuss their biological significance to the DDR.

MeSH Terms
Animals DNA Breaks DNA Repair/physiology Humans Mammals/genetics,metabolism Protein Processing, Post-Translational Proteins/metabolism Saccharomyces/genetics,metabolism Signal Transduction
Chemicals
Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Polo Sophie E
The Gurdon Institute, Department of Biochemistry, University of Cambridge, Cambridge CB21QN, United Kingdom.
Jackson Stephen P
References (363)
363 references, click to expand
  1. Distinct roles for the RSC and Swi/Snf ATP-dependent chromatin remodelers in DNA double-strand break repair.
    Genes Dev. 2005 Jul 15;19(14):1656-61 PMID: 16024655
  2. Interplay between Ino80 and Swr1 chromatin remodeling enzymes regulates cell cycle checkpoint adaptation in response to DNA damage.
    Genes Dev. 2006 Sep 1;20(17):2437-49 PMID: 16951256
  3. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway.
    Annu Rev Biochem. 2010;79:181-211 PMID: 20192759
  4. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions.
    Biochem J. 1999 Sep 1;342 ( Pt 2):249-68 PMID: 10455009
  5. Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions.
    Science. 2004 Dec 17;306(5704):2084-7 PMID: 15528408
  6. Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest.
    Proc Natl Acad Sci U S A. 1996 May 14;93(10):4827-32 PMID: 8643488
  7. Rnf8 deficiency impairs class switch recombination, spermatogenesis, and genomic integrity and predisposes for cancer.
    J Exp Med. 2010 May 10;207(5):983-97 PMID: 20385750
  8. How the fanconi anemia pathway guards the genome.
    Annu Rev Genet. 2009;43:223-49 PMID: 19686080
  9. High-resolution profiling of gammaH2AX around DNA double strand breaks in the mammalian genome.
    EMBO J. 2010 Apr 21;29(8):1446-57 PMID: 20360682
  10. Recruitment of the type B histone acetyltransferase Hat1p to chromatin is linked to DNA double-strand breaks.
    Mol Cell Biol. 2006 May;26(9):3649-58 PMID: 16612003
  11. Modulation of nucleosome-binding activity of FACT by poly(ADP-ribosyl)ation.
    Nucleic Acids Res. 2006 May 08;34(8):2398-407 PMID: 16682447
  12. Localized histone acetylation and deacetylation triggered by the homologous recombination pathway of double-strand DNA repair.
    Mol Cell Biol. 2005 Jun;25(12):4903-13 PMID: 15923609
  13. Analysis of ionizing radiation-induced foci of DNA damage repair proteins.
    Mutat Res. 2005 Jul 1;574(1-2):22-33 PMID: 15914204
  14. Highly efficient endogenous human gene correction using designed zinc-finger nucleases.
    Nature. 2005 Jun 2;435(7042):646-51 PMID: 15806097
  15. SOSS complexes participate in the maintenance of genomic stability.
    Mol Cell. 2009 Aug 14;35(3):384-93 PMID: 19683501
  16. Chromatin modifications and their function.
    Cell. 2007 Feb 23;128(4):693-705 PMID: 17320507
  17. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis.
    Nat Rev Mol Cell Biol. 2010 Mar;11(3):196-207 PMID: 20177395
  18. ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1.
    Mol Cell Biol. 2005 Jul;25(13):5363-79 PMID: 15964794
  19. Structural and functional analysis of the Crb2-BRCT2 domain reveals distinct roles in checkpoint signaling and DNA damage repair.
    Genes Dev. 2008 Aug 1;22(15):2034-47 PMID: 18676809
  20. MDC1: The art of keeping things in focus.
    Chromosoma. 2010 Aug;119(4):337-49 PMID: 20224865
  21. The ubiquitous role of ubiquitin in the DNA damage response.
    DNA Repair (Amst). 2010 Dec 10;9(12):1229-40 PMID: 21056014
  22. Histone ubiquitination associates with BRCA1-dependent DNA damage response.
    Mol Cell Biol. 2009 Feb;29(3):849-60 PMID: 19015238
  23. H2AX haploinsufficiency modifies genomic stability and tumor susceptibility.
    Cell. 2003 Aug 8;114(3):371-383 PMID: 12914701
  24. AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching.
    Nature. 2001 Dec 6;414(6864):660-665 PMID: 11740565
  25. The GAR motif of 53BP1 is arginine methylated by PRMT1 and is necessary for 53BP1 DNA binding activity.
    Cell Cycle. 2005 Dec;4(12):1834-41 PMID: 16294045
  26. Mapping of protein-protein interactions within the DNA-dependent protein kinase complex.
    Nucleic Acids Res. 1999 Sep 1;27(17):3494-502 PMID: 10446239
  27. Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents.
    Cell. 2010 Jul 9;142(1):77-88 PMID: 20603016
  28. DNA damage foci at dysfunctional telomeres.
    Curr Biol. 2003 Sep 2;13(17):1549-56 PMID: 12956959
  29. hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex.
    Nucleic Acids Res. 2011 Mar;39(5):1692-702 PMID: 21051358
  30. Linkage-specific avidity defines the lysine 63-linked polyubiquitin-binding preference of rap80.
    Mol Cell. 2009 Mar 27;33(6):775-83 PMID: 19328070
  31. Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast.
    Mol Cell Biol. 2004 Jul;24(14):6215-30 PMID: 15226425
  32. Human Xip1 (C2orf13) is a novel regulator of cellular responses to DNA strand breaks.
    J Biol Chem. 2007 Jul 6;282(27):19638-43 PMID: 17507382
  33. Taking the time to make important decisions: the checkpoint effector kinases Chk1 and Chk2 and the DNA damage response.
    DNA Repair (Amst). 2009 Sep 2;8(9):1047-54 PMID: 19473886
  34. Spatiotemporal dynamics of regulatory protein recruitment at DNA damage sites.
    J Cell Biochem. 2008 Aug 1;104(5):1562-9 PMID: 18384127
  35. GammaH2AX and cancer.
    Nat Rev Cancer. 2008 Dec;8(12):957-67 PMID: 19005492
  36. The expanding field of poly(ADP-ribosyl)ation reactions. 'Protein Modifications: Beyond the Usual Suspects' Review Series.
    EMBO Rep. 2008 Nov;9(11):1094-100 PMID: 18927583
  37. Methylation of MRE11 regulates its nuclear compartmentalization.
    Cell Cycle. 2005 Jul;4(7):981-9 PMID: 15970667
  38. A role for Saccharomyces cerevisiae histone H2A in DNA repair.
    Nature. 2000 Dec 21-28;408(6815):1001-4 PMID: 11140636
  39. ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin.
    Mol Cell. 2008 Jul 25;31(2):167-77 PMID: 18657500
  40. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery.
    Nature. 2006 Jan 26;439(7075):497-501 PMID: 16299494
  41. SnapShot: Homologous recombination in DNA double-strand break repair.
    Cell. 2010 Aug 20;142(4):646, 646.e1 PMID: 20723763
  42. The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA.
    Nat Struct Mol Biol. 2010 Oct;17(10):1263-5 PMID: 20729858
  43. Mechanism of eukaryotic homologous recombination.
    Annu Rev Biochem. 2008;77:229-57 PMID: 18275380
  44. ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks.
    Cell. 2010 Jun 11;141(6):970-81 PMID: 20550933
  45. INO80 and gamma-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair.
    Cell. 2004 Dec 17;119(6):767-75 PMID: 15607974
  46. Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage.
    Cell. 1997 Aug 8;90(3):425-35 PMID: 9267023
  47. Control of Rad52 recombination activity by double-strand break-induced SUMO modification.
    Nat Cell Biol. 2006 Nov;8(11):1284-90 PMID: 17013376
  48. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2.
    Mol Cell. 2006 Jun 23;22(6):719-729 PMID: 16793542
  49. Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks.
    Cell. 2006 Nov 3;127(3):509-22 PMID: 17081974
  50. Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair.
    Mol Cell. 2004 Dec 22;16(6):1003-15 PMID: 15610742
  51. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.
    Science. 2007 May 25;316(5828):1160-6 PMID: 17525332
  52. SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging.
    Cell. 2008 Nov 28;135(5):907-18 PMID: 19041753
  53. Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks.
    J Cell Biol. 2007 Apr 23;177(2):219-29 PMID: 17438073
  54. Site-specific phosphorylation dynamics of the nuclear proteome during the DNA damage response.
    Mol Cell Proteomics. 2010 Jun;9(6):1314-23 PMID: 20164059
  55. Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition.
    Oncogene. 2010 Apr 15;29(15):2281-91 PMID: 20101220
  56. A role for the deubiquitinating enzyme USP28 in control of the DNA-damage response.
    Cell. 2006 Aug 11;126(3):529-42 PMID: 16901786
  57. Single-stranded DNA-binding protein hSSB1 is critical for genomic stability.
    Nature. 2008 May 29;453(7195):677-81 PMID: 18449195
  58. Poly(ADP-ribosylation) in vitro. Reaction parameters and enzyme mechanism.
    J Biol Chem. 1982 Jul 10;257(13):7808-13 PMID: 6282854
  59. Deciphering the chromatin landscape induced around DNA double strand breaks.
    Cell Cycle. 2010 Aug 1;9(15):2963-72 PMID: 20714222
  60. UMI, a novel RNF168 ubiquitin binding domain involved in the DNA damage signaling pathway.
    Mol Cell Biol. 2011 Jan;31(1):118-26 PMID: 21041483
  61. From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair.
    FEBS Lett. 1997 Jan 2;400(1):25-30 PMID: 9000507
  62. DNA double-strand breaks in meiosis: checking their formation, processing and repair.
    DNA Repair (Amst). 2009 Sep 2;8(9):1127-38 PMID: 19464965
  63. Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining.
    Nat Struct Mol Biol. 2010 Sep;17(9):1144-51 PMID: 20802485
  64. When the caps fall off: responses to telomere uncapping in yeast.
    FEBS Lett. 2010 Sep 10;584(17):3734-40 PMID: 20600003
  65. Phospho-dependent interactions between NBS1 and MDC1 mediate chromatin retention of the MRN complex at sites of DNA damage.
    EMBO Rep. 2008 Aug;9(8):795-801 PMID: 18583988
  66. The FHA domain is a modular phosphopeptide recognition motif.
    Mol Cell. 1999 Sep;4(3):387-94 PMID: 10518219
  67. Ku recruits the XRCC4-ligase IV complex to DNA ends.
    Mol Cell Biol. 2000 May;20(9):2996-3003 PMID: 10757784
  68. Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60.
    Nat Cell Biol. 2009 Nov;11(11):1376-82 PMID: 19783983
  69. Chromatin architectural proteins.
    Chromosome Res. 2006;14(1):39-51 PMID: 16506095
  70. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage.
    Nature. 2005 Mar 31;434(7033):605-11 PMID: 15758953
  71. Role of mammalian Mre11 in classical and alternative nonhomologous end joining.
    Nat Struct Mol Biol. 2009 Aug;16(8):814-8 PMID: 19633669
  72. Solution structure of a zinc-finger domain that binds to poly-ADP-ribose.
    Genes Cells. 2010 Feb;15(2):101-10 PMID: 20088964
  73. INTS3 controls the hSSB1-mediated DNA damage response.
    J Cell Biol. 2009 Oct 5;187(1):25-32 PMID: 19786574
  74. Human CtIP promotes DNA end resection.
    Nature. 2007 Nov 22;450(7169):509-14 PMID: 17965729
  75. The macro domain is an ADP-ribose binding module.
    EMBO J. 2005 Jun 1;24(11):1911-20 PMID: 15902274
  76. Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites.
    Mol Cell. 2004 Dec 22;16(6):979-90 PMID: 15610740
  77. SnapShot: The SUMO system.
    Cell. 2010 Nov 24;143(5):848-848.e1 PMID: 21111242
  78. The ATM repair pathway inhibits RNA polymerase I transcription in response to chromosome breaks.
    Nature. 2007 Jun 7;447(7145):730-4 PMID: 17554310
  79. MCPH1 functions in an H2AX-dependent but MDC1-independent pathway in response to DNA damage.
    J Biol Chem. 2007 Nov 30;282(48):35416-23 PMID: 17925396
  80. At loose ends: resecting a double-strand break.
    Cell. 2009 May 29;137(5):807-10 PMID: 19490890
  81. The DNA-dependent protein kinase is inactivated by autophosphorylation of the catalytic subunit.
    J Biol Chem. 1996 Apr 12;271(15):8936-41 PMID: 8621537
  82. Recruitment of DNA methyltransferase I to DNA repair sites.
    Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8905-9 PMID: 15956212
  83. A plant homeodomain in RAG-2 that binds Hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangement.
    Immunity. 2007 Oct;27(4):561-71 PMID: 17936034
  84. Chromosomal association of the Smc5/6 complex reveals that it functions in differently regulated pathways.
    Mol Cell. 2006 Jun 23;22(6):755-767 PMID: 16793545
  85. The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus.
    Nat Cell Biol. 2007 Aug;9(8):923-31 PMID: 17643116
  86. RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites.
    Science. 2007 May 25;316(5828):1198-202 PMID: 17525341
  87. PP4 is a gamma H2AX phosphatase required for recovery from the DNA damage checkpoint.
    EMBO Rep. 2008 Oct;9(10):1019-26 PMID: 18758438
  88. DNA damage and decisions: CtIP coordinates DNA repair and cell cycle checkpoints.
    Trends Cell Biol. 2010 Jul;20(7):402-9 PMID: 20444606
  89. Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase.
    Science. 2008 Oct 24;322(5901):597-602 PMID: 18948542
  90. A glycine-arginine domain in control of the human MRE11 DNA repair protein.
    Mol Cell Biol. 2008 May;28(9):3058-69 PMID: 18285453
  91. RNF168, a new RING finger, MIU-containing protein that modifies chromatin by ubiquitination of histones H2A and H2AX.
    BMC Mol Biol. 2009 Jun 05;10:55 PMID: 19500350
  92. Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair.
    Cell. 2006 Dec 29;127(7):1361-73 PMID: 17190600
  93. Ku autoantigen is the regulatory component of a template-associated protein kinase that phosphorylates RNA polymerase II.
    Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11920-4 PMID: 1465419
  94. A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization.
    Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4777-82 PMID: 15738391
  95. HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes.
    Nat Cell Biol. 2010 Jan;12(1):80-6; sup pp 1-12 PMID: 20023648
  96. Live cell imaging of heavy-ion-induced radiation responses by beamline microscopy.
    Radiat Res. 2005 Jun;163(6):681-90 PMID: 15913400
  97. Nucleases and helicases take center stage in homologous recombination.
    Trends Biochem Sci. 2009 May;34(5):264-72 PMID: 19375328
  98. A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses.
    EMBO J. 2007 Apr 18;26(8):2094-103 PMID: 17396150
  99. BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair.
    Hum Mol Genet. 2004 Apr 15;13(8):807-17 PMID: 14976165
  100. Bovine thymus poly(adenosine diphosphate ribose) polymerase. Physical properties and binding to DNA.
    J Biol Chem. 1980 Jul 10;255(13):6205-11 PMID: 6248513
  101. DNA repair: easy to visualize, difficult to elucidate.
    Trends Cell Biol. 2009 Nov;19(11):617-29 PMID: 19819145
  102. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly.
    Cell. 2007 Nov 30;131(5):901-14 PMID: 18001825
  103. Chromosome breakage after G2 checkpoint release.
    J Cell Biol. 2007 Mar 12;176(6):749-55 PMID: 17353355
  104. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.
    Science. 2003 Jun 6;300(5625):1542-8 PMID: 12791985
  105. Principles of ubiquitin and SUMO modifications in DNA repair.
    Nature. 2009 Mar 26;458(7237):461-7 PMID: 19325626
  106. Local DNA damage by proton microbeam irradiation induces poly(ADP-ribose) synthesis in mammalian cells.
    Mutagenesis. 2003 Sep;18(5):411-6 PMID: 12960408
  107. SnapShot: Nonhomologous DNA end joining (NHEJ).
    Cell. 2010 Aug 6;142(3):496-496.e1 PMID: 20691907
  108. Function of a conserved checkpoint recruitment domain in ATRIP proteins.
    Mol Cell Biol. 2007 May;27(9):3367-77 PMID: 17339343
  109. Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks.
    J Cell Biol. 2006 Mar 13;172(6):823-34 PMID: 16520385
  110. Dual chromatin remodeling roles for RSC during DNA double strand break induction and repair at the yeast MAT locus.
    J Biol Chem. 2007 Sep 21;282(38):27693-701 PMID: 17652077
  111. hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks.
    Mol Cell Biol. 1997 Oct;17(10):6087-96 PMID: 9315668
  112. Heterochromatin protein 1 is recruited to various types of DNA damage.
    J Cell Biol. 2009 May 18;185(4):577-86 PMID: 19451271
  113. Monoubiquitylation in the Fanconi anemia DNA damage response pathway.
    DNA Repair (Amst). 2009 Apr 5;8(4):430-5 PMID: 19264559
  114. Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA.
    Nature. 2005 Sep 15;437(7057):440-3 PMID: 16163361
  115. Regulation of DNA repair through deSUMOylation and SUMOylation of replication protein A complex.
    Mol Cell. 2010 Aug 13;39(3):333-45 PMID: 20705237
  116. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair.
    Nature. 2001 Aug 9;412(6847):607-14 PMID: 11493912
  117. Single-strand break repair and genetic disease.
    Nat Rev Genet. 2008 Aug;9(8):619-31 PMID: 18626472
  118. Dynamic assembly of end-joining complexes requires interaction between Ku70/80 and XRCC4.
    Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18597-602 PMID: 17124166
  119. Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1.
    Science. 2009 Sep 4;325(5945):1240-3 PMID: 19661379
  120. Checkpoint mechanisms at the intersection between DNA damage and repair.
    DNA Repair (Amst). 2009 Sep 2;8(9):1055-67 PMID: 19497792
  121. 53BP1 is required for class switch recombination.
    J Cell Biol. 2004 May 24;165(4):459-64 PMID: 15159415
  122. Repair of endogenous DNA damage.
    Cold Spring Harb Symp Quant Biol. 2000;65:127-33 PMID: 12760027
  123. Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8.
    J Exp Med. 2010 May 10;207(5):973-81 PMID: 20385748
  124. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks.
    Nat Cell Biol. 2003 Jul;5(7):675-9 PMID: 12792649
  125. A chromatin localization screen reveals poly (ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage.
    Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18475-80 PMID: 20937877
  126. In situ visualization of DNA double-strand break repair in human fibroblasts.
    Science. 1998 Apr 24;280(5363):590-2 PMID: 9554850
  127. Mislocalization of the MRN complex prevents ATR signaling during adenovirus infection.
    EMBO J. 2009 Mar 18;28(6):652-62 PMID: 19197236
  128. Heterochromatin is refractory to gamma-H2AX modification in yeast and mammals.
    J Cell Biol. 2007 Jul 16;178(2):209-18 PMID: 17635934
  129. Crosstalk between histone modifications during the DNA damage response.
    Trends Cell Biol. 2009 May;19(5):207-17 PMID: 19342239
  130. BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP.
    Genes Dev. 2006 Jul 1;20(13):1721-6 PMID: 16818604
  131. Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX.
    Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8173-8 PMID: 12034884
  132. Structure of chromatin.
    Annu Rev Biochem. 1977;46:931-54 PMID: 332067
  133. The expanding role of poly(ADP-ribose) metabolism: current challenges and new perspectives.
    Curr Opin Cell Biol. 2006 Apr;18(2):145-51 PMID: 16516457
  134. Accumulation of Pax2 transactivation domain interaction protein (PTIP) at sites of DNA breaks via RNF8-dependent pathway is required for cell survival after DNA damage.
    J Biol Chem. 2009 Mar 13;284(11):7284-93 PMID: 19124460
  135. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks.
    Nat Cell Biol. 2006 Jan;8(1):37-45 PMID: 16327781
  136. The emerging role of nuclear architecture in DNA repair and genome maintenance.
    Nat Rev Mol Cell Biol. 2009 Apr;10(4):243-54 PMID: 19277046
  137. Human USP3 is a chromatin modifier required for S phase progression and genome stability.
    Curr Biol. 2007 Nov 20;17(22):1972-7 PMID: 17980597
  138. Rad52 SUMOylation affects the efficiency of the DNA repair.
    Nucleic Acids Res. 2010 Aug;38(14):4708-21 PMID: 20371517
  139. HSSB1 and hSSB2 form similar multiprotein complexes that participate in DNA damage response.
    J Biol Chem. 2009 Aug 28;284(35):23525-31 PMID: 19605351
  140. gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair.
    Mol Cell. 2005 Dec 9;20(5):801-9 PMID: 16310392
  141. The p400 ATPase regulates nucleosome stability and chromatin ubiquitination during DNA repair.
    J Cell Biol. 2010 Oct 4;191(1):31-43 PMID: 20876283
  142. The biology of chromatin remodeling complexes.
    Annu Rev Biochem. 2009;78:273-304 PMID: 19355820
  143. DNA-dependent protein kinase and XRCC4-DNA ligase IV mobilization in the cell in response to DNA double strand breaks.
    J Biol Chem. 2005 Feb 25;280(8):7060-9 PMID: 15520013
  144. The complexity of phosphorylated H2AX foci formation and DNA repair assembly at DNA double-strand breaks.
    Cell Cycle. 2010 Jan 15;9(2):389-97 PMID: 20046100
  145. DNA double-strand breaks trigger genome-wide sister-chromatid cohesion through Eco1 (Ctf7).
    Science. 2007 Jul 13;317(5835):245-8 PMID: 17626885
  146. Ku and DNA-dependent protein kinase dynamic conformations and assembly regulate DNA binding and the initial non-homologous end joining complex.
    J Biol Chem. 2010 Jan 8;285(2):1414-23 PMID: 19893054
  147. Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells.
    Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7303-7 PMID: 9207086
  148. RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination.
    Nature. 2007 Dec 13;450(7172):1106-10 PMID: 18033247
  149. Feedback-regulated poly(ADP-ribosyl)ation by PARP-1 is required for rapid response to DNA damage in living cells.
    Nucleic Acids Res. 2007;35(22):7665-75 PMID: 17982172
  150. DNA damage checkpoints: from initiation to recovery or adaptation.
    Curr Opin Cell Biol. 2007 Apr;19(2):238-45 PMID: 17303408
  151. Imaging of protein movement induced by chromosomal breakage: tiny 'local' lesions pose great 'global' challenges.
    Chromosoma. 2005 Aug;114(3):146-54 PMID: 15988581
  152. Genomic instability in mice lacking histone H2AX.
    Science. 2002 May 3;296(5569):922-7 PMID: 11934988
  153. New histone incorporation marks sites of UV repair in human cells.
    Cell. 2006 Nov 3;127(3):481-93 PMID: 17081972
  154. Structure and identification of ADP-ribose recognition motifs of APLF and role in the DNA damage response.
    Proc Natl Acad Sci U S A. 2010 May 18;107(20):9129-34 PMID: 20439749
  155. Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors.
    Cell. 2003 Aug 8;114(3):359-70 PMID: 12914700
  156. Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA.
    Nat Struct Mol Biol. 2010 Oct;17(10):1260-2 PMID: 20729859
  157. RAD18 transmits DNA damage signalling to elicit homologous recombination repair.
    Nat Cell Biol. 2009 May;11(5):592-603 PMID: 19396164
  158. PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites.
    J Biol Chem. 2008 Jan 11;283(2):1197-208 PMID: 18025084
  159. The mammalian INO80 complex is recruited to DNA damage sites in an ARP8 dependent manner.
    Biochem Biophys Res Commun. 2010 Nov 26;402(4):619-25 PMID: 20971067
  160. Watching individual proteins acting on single molecules of DNA.
    Methods Enzymol. 2010;472:261-91 PMID: 20580968
  161. Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break.
    Curr Biol. 2004 Oct 5;14(19):1703-11 PMID: 15458641
  162. A CAF-1-PCNA-mediated chromatin assembly pathway triggered by sensing DNA damage.
    Mol Cell Biol. 2000 Feb;20(4):1206-18 PMID: 10648606
  163. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress.
    J Biol Chem. 2001 Dec 21;276(51):47759-62 PMID: 11673449
  164. Positional stability of single double-strand breaks in mammalian cells.
    Nat Cell Biol. 2007 Jun;9(6):675-82 PMID: 17486118
  165. The DNA-damage response in human biology and disease.
    Nature. 2009 Oct 22;461(7267):1071-8 PMID: 19847258
  166. PALB2 is an integral component of the BRCA complex required for homologous recombination repair.
    Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7155-60 PMID: 19369211
  167. 53BP1-dependent robust localized KAP-1 phosphorylation is essential for heterochromatic DNA double-strand break repair.
    Nat Cell Biol. 2010 Feb;12(2):177-84 PMID: 20081839
  168. A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA damage sites.
    EMBO J. 2006 May 17;25(10):2178-88 PMID: 16628214
  169. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks.
    Cell. 2005 Dec 29;123(7):1213-26 PMID: 16377563
  170. Mechanisms underlying ubiquitination.
    Annu Rev Biochem. 2001;70:503-33 PMID: 11395416
  171. Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment.
    J Mol Biol. 2003 Feb 7;326(1):93-103 PMID: 12547193
  172. Recruitment of phosphorylated NPM1 to sites of DNA damage through RNF8-dependent ubiquitin conjugates.
    Cancer Res. 2010 Sep 1;70(17):6746-56 PMID: 20713529
  173. PALB2 links BRCA1 and BRCA2 in the DNA-damage response.
    Curr Biol. 2009 Mar 24;19(6):524-9 PMID: 19268590
  174. DDK phosphorylates checkpoint clamp component Rad9 and promotes its release from damaged chromatin.
    Mol Cell. 2010 Nov 24;40(4):606-18 PMID: 21095590
  175. The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit.
    Mol Cell Biol. 1999 May;19(5):3267-77 PMID: 10207052
  176. Differential regulation of the cellular response to DNA double-strand breaks in G1.
    Mol Cell. 2008 Apr 11;30(1):73-85 PMID: 18406328
  177. Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler.
    Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13770-4 PMID: 19666485
  178. Chromatin remodelling at a DNA double-strand break site in Saccharomyces cerevisiae.
    Nature. 2005 Nov 17;438(7066):379-83 PMID: 16292314
  179. Docking onto chromatin via the Saccharomyces cerevisiae Rad9 Tudor domain.
    Yeast. 2007 Feb;24(2):105-19 PMID: 17243194
  180. Human Rad50/Mre11 is a flexible complex that can tether DNA ends.
    Mol Cell. 2001 Nov;8(5):1129-35 PMID: 11741547
  181. Mechanisms of double-strand break repair in somatic mammalian cells.
    Biochem J. 2009 Sep 25;423(2):157-68 PMID: 19772495
  182. ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex.
    Science. 2005 Apr 22;308(5721):551-4 PMID: 15790808
  183. A cooperative activation loop among SWI/SNF, gamma-H2AX and H3 acetylation for DNA double-strand break repair.
    EMBO J. 2010 Apr 21;29(8):1434-45 PMID: 20224553
  184. Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting gamma-H2AX induction.
    EMBO J. 2006 Sep 6;25(17):3986-97 PMID: 16932743
  185. Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80.
    EMBO J. 2009 Aug 19;28(16):2461-8 PMID: 19536136
  186. Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase.
    Science. 2007 Dec 7;318(5856):1637-40 PMID: 18006705
  187. GammaH2AX as a molecular marker of aging and disease.
    Epigenetics. 2010 Feb 16;5(2):129-36 PMID: 20150765
  188. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins.
    FASEB J. 1997 Jan;11(1):68-76 PMID: 9034168
  189. ATM-dependent and -independent dynamics of the nuclear phosphoproteome after DNA damage.
    Sci Signal. 2010 Dec 07;3(151):rs3 PMID: 21139141
  190. Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair.
    Cell. 2008 Oct 3;135(1):97-109 PMID: 18854158
  191. Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism.
    Annu Rev Biochem. 1997;66:61-92 PMID: 9242902
  192. The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks.
    Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3166-71 PMID: 19202061
  193. Dynamic changes in Rad51 distribution on chromatin during meiosis in male and female vertebrates.
    Chromosoma. 1995 Oct;104(1):19-28 PMID: 7587590
  194. MOF and H4 K16 acetylation play important roles in DNA damage repair by modulating recruitment of DNA damage repair protein Mdc1.
    Mol Cell Biol. 2010 Nov;30(22):5335-47 PMID: 20837706
  195. Requirement of the MRN complex for ATM activation by DNA damage.
    EMBO J. 2003 Oct 15;22(20):5612-21 PMID: 14532133
  196. MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings.
    Trends Genet. 2008 Nov;24(11):529-38 PMID: 18809224
  197. A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair.
    Mol Cell. 2010 Jul 9;39(1):36-47 PMID: 20603073
  198. Requirement for the phospho-H2AX binding module of Crb2 in double-strand break targeting and checkpoint activation.
    Mol Cell Biol. 2010 Oct;30(19):4722-31 PMID: 20679488
  199. Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2.
    Cell. 2010 Jul 9;142(1):65-76 PMID: 20603015
  200. A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage.
    Nucleic Acids Res. 2003 Oct 1;31(19):5526-33 PMID: 14500814
  201. Assessment of protein dynamics and DNA repair following generation of DNA double-strand breaks at defined genomic sites.
    Nat Protoc. 2008;3(5):915-22 PMID: 18451799
  202. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation.
    Cancer Res. 2004 Apr 1;64(7):2390-6 PMID: 15059890
  203. BRCA1 and its toolbox for the maintenance of genome integrity.
    Nat Rev Mol Cell Biol. 2010 Feb;11(2):138-48 PMID: 20029420
  204. Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells.
    J Cell Biol. 2005 Aug 1;170(3):341-7 PMID: 16061690
  205. Control of sister chromatid recombination by histone H2AX.
    Mol Cell. 2004 Dec 22;16(6):1017-25 PMID: 15610743
  206. Di-methyl H4 lysine 20 targets the checkpoint protein Crb2 to sites of DNA damage.
    J Biol Chem. 2008 Nov 28;283(48):33168-74 PMID: 18826944
  207. PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and BRCA2.
    Mol Cancer Res. 2009 Jul;7(7):1110-8 PMID: 19584259
  208. MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to DNA double-strand breaks.
    Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11200-5 PMID: 18678890
  209. Induction of linear tracks of DNA double-strand breaks by alpha-particle irradiation of cells.
    Nat Methods. 2008 Mar;5(3):261-6 PMID: 18309310
  210. Constitutive phosphorylation of MDC1 physically links the MRE11-RAD50-NBS1 complex to damaged chromatin.
    J Cell Biol. 2008 Apr 21;181(2):227-40 PMID: 18411308
  211. ATM and the Mre11 complex combine to recognize and signal DNA double-strand breaks.
    Oncogene. 2007 Dec 10;26(56):7749-58 PMID: 18066087
  212. Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination.
    Nat Cell Biol. 2006 Sep;8(9):1032-4 PMID: 16892052
  213. A divalent FHA/BRCT-binding mechanism couples the MRE11-RAD50-NBS1 complex to damaged chromatin.
    EMBO Rep. 2010 May;11(5):387-92 PMID: 20224574
  214. Focus on histone variant H2AX: to be or not to be.
    FEBS Lett. 2010 Sep 10;584(17):3717-24 PMID: 20493860
  215. gammaH2AX foci form preferentially in euchromatin after ionising-radiation.
    PLoS One. 2007 Oct 24;2(10):e1057 PMID: 17957241
  216. HP1-beta mobilization promotes chromatin changes that initiate the DNA damage response.
    Nature. 2008 May 29;453(7195):682-6 PMID: 18438399
  217. Human SIRT6 promotes DNA end resection through CtIP deacetylation.
    Science. 2010 Sep 10;329(5997):1348-53 PMID: 20829486
  218. Mice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease.
    Genes Dev. 1995 Mar 1;9(5):509-20 PMID: 7698643
  219. Analysis of DNA recombination and repair proteins in living cells by photobleaching microscopy.
    Methods Enzymol. 2006;408:463-85 PMID: 16793387
  220. Recruitment of the INO80 complex by H2A phosphorylation links ATP-dependent chromatin remodeling with DNA double-strand break repair.
    Cell. 2004 Dec 17;119(6):777-88 PMID: 15607975
  221. Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin.
    J Cell Biol. 2008 Apr 21;181(2):213-26 PMID: 18411307
  222. A macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation.
    Nat Struct Mol Biol. 2009 Sep;16(9):923-9 PMID: 19680243
  223. A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replication.
    Mol Cell. 2008 Jul 11;31(1):33-46 PMID: 18614045
  224. Rapid PIKK-dependent release of Chk1 from chromatin promotes the DNA-damage checkpoint response.
    Curr Biol. 2006 Jan 24;16(2):150-9 PMID: 16360315
  225. The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway.
    Mol Cell. 2005 Feb 4;17(3):331-9 PMID: 15694335
  226. Functional interaction between PARP-1 and PARP-2 in chromosome stability and embryonic development in mouse.
    EMBO J. 2003 May 1;22(9):2255-63 PMID: 12727891
  227. Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair.
    Cell. 2009 Oct 2;139(1):87-99 PMID: 19804755
  228. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins.
    Cell. 2007 Nov 30;131(5):887-900 PMID: 18001824
  229. Wip1 directly dephosphorylates gamma-H2AX and attenuates the DNA damage response.
    Cancer Res. 2010 May 15;70(10):4112-22 PMID: 20460517
  230. Microcollimator for micrometer-wide stripe irradiation of cells using 20-30 keV X rays.
    Radiat Res. 2009 Aug;172(2):252-9 PMID: 19630530
  231. FACT-mediated exchange of histone variant H2AX regulated by phosphorylation of H2AX and ADP-ribosylation of Spt16.
    Mol Cell. 2008 Apr 11;30(1):86-97 PMID: 18406329
  232. Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes.
    Nucleic Acids Res. 2008 Dec;36(22):6959-76 PMID: 18981049
  233. RSC mobilizes nucleosomes to improve accessibility of repair machinery to the damaged chromatin.
    Mol Cell Biol. 2007 Mar;27(5):1602-13 PMID: 17178837
  234. Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response.
    Science. 2007 May 25;316(5828):1202-5 PMID: 17525342
  235. Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair.
    Cell. 2008 Jul 25;134(2):231-43 PMID: 18662539
  236. Repair of DNA double strand breaks: in vivo biochemistry.
    Methods Enzymol. 2006;408:416-29 PMID: 16793384
  237. The DNA damage response: ten years after.
    Mol Cell. 2007 Dec 14;28(5):739-45 PMID: 18082599
  238. Lethality induced by a single site-specific double-strand break in a dispensable yeast plasmid.
    Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5613-7 PMID: 8516308
  239. Mechanism of interaction between Ku protein and DNA.
    J Biol Chem. 1986 Aug 5;261(22):10375-9 PMID: 3015926
  240. Spatial and temporal cellular responses to single-strand breaks in human cells.
    Mol Cell Biol. 2003 Jun;23(11):3974-81 PMID: 12748298
  241. Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification.
    Hum Mol Genet. 2005 May 15;14(10):1351-65 PMID: 15829507
  242. FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair.
    Science. 2010 Aug 6;329(5992):693-6 PMID: 20671156
  243. Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks.
    J Cell Biol. 2006 Apr 24;173(2):195-206 PMID: 16618811
  244. HP1: a functionally multifaceted protein.
    Curr Opin Genet Dev. 2008 Apr;18(2):169-74 PMID: 18329871
  245. The nucleosome: a little variation goes a long way.
    Biochem Cell Biol. 2006 Aug;84(4):505-17 PMID: 16936823
  246. Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage.
    Nat Cell Biol. 2003 Mar;5(3):255-60 PMID: 12598907
  247. Zinc-binding domain of poly(ADP-ribose)polymerase participates in the recognition of single strand breaks on DNA.
    J Mol Biol. 1989 Nov 5;210(1):229-33 PMID: 2511329
  248. Assembly of checkpoint and repair machineries at DNA damage sites.
    Trends Biochem Sci. 2010 Feb;35(2):101-8 PMID: 19875294
  249. Oligonucleotide/oligosaccharide-binding fold proteins: a growing family of genome guardians.
    Crit Rev Biochem Mol Biol. 2010 Aug;45(4):266-75 PMID: 20515430
  250. Positional stability of damaged chromatin domains along radiation tracks in mammalian cells.
    Radiat Res. 2009 Apr;171(4):405-18 PMID: 19397441
  251. PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase.
    J Biol Chem. 1999 Jun 18;274(25):17860-8 PMID: 10364231
  252. Structure of the BRCT repeat domain of MDC1 and its specificity for the free COOH-terminal end of the gamma-H2AX histone tail.
    J Biol Chem. 2005 Sep 16;280(37):32053-6 PMID: 16049003
  253. Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins.
    Cell. 2004 Sep 17;118(6):699-713 PMID: 15369670
  254. Functional human telomeres are recognized as DNA damage in G2 of the cell cycle.
    Mol Cell. 2005 Nov 23;20(4):551-61 PMID: 16307919
  255. Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks.
    Nature. 2004 Nov 18;432(7015):406-11 PMID: 15525939
  256. Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island.
    PLoS Genet. 2008 Aug 15;4(8):e1000155 PMID: 18704159
  257. The yeast chromatin remodeler RSC complex facilitates end joining repair of DNA double-strand breaks.
    Mol Cell Biol. 2005 May;25(10):3934-44 PMID: 15870268
  258. Poly(ADP-ribose) binds to specific domains in DNA damage checkpoint proteins.
    J Biol Chem. 2000 Dec 29;275(52):40974-80 PMID: 11016934
  259. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals.
    Mol Cell. 2006 Jan 20;21(2):187-200 PMID: 16427009
  260. DNA damage, homology-directed repair, and DNA methylation.
    PLoS Genet. 2007 Jul;3(7):e110 PMID: 17616978
  261. Ku recruits XLF to DNA double-strand breaks.
    EMBO Rep. 2008 Jan;9(1):91-6 PMID: 18064046
  262. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins.
    Cell. 2009 Feb 6;136(3):435-46 PMID: 19203579
  263. Evolutionary history of the poly(ADP-ribose) polymerase gene family in eukaryotes.
    BMC Evol Biol. 2010 Oct 13;10:308 PMID: 20942953
  264. Use of near infrared femtosecond lasers as sub-micron radiation microbeam for cell DNA damage and repair studies.
    Mutat Res. 2010 Apr-Jun;704(1-3):38-44 PMID: 20079460
  265. A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses.
    EMBO J. 2010 Mar 3;29(5):943-55 PMID: 20075863
  266. Function of poly(ADP-ribose) polymerase in response to DNA damage: gene-disruption study in mice.
    Mol Cell Biochem. 1999 Mar;193(1-2):149-52 PMID: 10331651
  267. Dial 9-1-1 for DNA damage: the Rad9-Hus1-Rad1 (9-1-1) clamp complex.
    DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1009-14 PMID: 15279787
  268. Regulation of the histone H4 monomethylase PR-Set7 by CRL4(Cdt2)-mediated PCNA-dependent degradation during DNA damage.
    Mol Cell. 2010 Nov 12;40(3):364-76 PMID: 21035370
  269. Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins.
    Nature. 2008 Jan 3;451(7174):81-5 PMID: 18172500
  270. WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity.
    Nature. 2009 Jan 1;457(7225):57-62 PMID: 19092802
  271. Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks.
    Nat Cell Biol. 2006 Jan;8(1):91-9 PMID: 16341205
  272. RAD18 promotes DNA double-strand break repair during G1 phase through chromatin retention of 53BP1.
    Nucleic Acids Res. 2009 Apr;37(7):2176-93 PMID: 19228710
  273. Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage.
    Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20759-63 PMID: 18077395
  274. The emerging role of HP1 in the DNA damage response.
    Mol Cell Biol. 2009 Dec;29(24):6335-40 PMID: 19805510
  275. 53BP1 facilitates long-range DNA end-joining during V(D)J recombination.
    Nature. 2008 Nov 27;456(7221):529-33 PMID: 18931658
  276. The NuRD chromatin-remodeling complex regulates signaling and repair of DNA damage.
    J Cell Biol. 2010 Sep 6;190(5):741-9 PMID: 20805320
  277. Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4.
    EMBO J. 2010 Sep 15;29(18):3130-9 PMID: 20693977
  278. Chromosome-wide Rad51 spreading and SUMO-H2A.Z-dependent chromosome fixation in response to a persistent DNA double-strand break.
    Mol Cell. 2009 Feb 13;33(3):335-43 PMID: 19217407
  279. Genome maintenance mechanisms for preventing cancer.
    Nature. 2001 May 17;411(6835):366-74 PMID: 11357144
  280. Subdiffraction multicolor imaging of the nuclear periphery with 3D structured illumination microscopy.
    Science. 2008 Jun 6;320(5881):1332-6 PMID: 18535242
  281. Surviving the breakup: the DNA damage checkpoint.
    Annu Rev Genet. 2006;40:209-35 PMID: 16805667
  282. Mechanisms and regulation of DNA end resection.
    EMBO J. 2010 Sep 1;29(17):2864-74 PMID: 20647996
  283. The DNA damage response: making it safe to play with knives.
    Mol Cell. 2010 Oct 22;40(2):179-204 PMID: 20965415
  284. PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways.
    Nucleic Acids Res. 2006;34(21):6170-82 PMID: 17088286
  285. BRCA1 associates with the inactive X chromosome in late S-phase, coupled with transient H2AX phosphorylation.
    Chromosoma. 2005 Dec;114(6):432-9 PMID: 16240122
  286. Dephosphorylation of histone gamma-H2AX during repair of DNA double-strand breaks in mammalian cells and its inhibition by calyculin A.
    Radiat Res. 2003 Sep;160(3):309-17 PMID: 12926989
  287. APLF (C2orf13) is a novel component of poly(ADP-ribose) signaling in mammalian cells.
    Mol Cell Biol. 2008 Jul;28(14):4620-8 PMID: 18474613
  288. Rad9 BRCT domain interaction with phosphorylated H2AX regulates the G1 checkpoint in budding yeast.
    EMBO Rep. 2007 Sep;8(9):851-7 PMID: 17721446
  289. Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response.
    J Cell Biol. 2003 Mar 31;160(7):1017-27 PMID: 12668657
  290. CDK targets Sae2 to control DNA-end resection and homologous recombination.
    Nature. 2008 Oct 2;455(7213):689-92 PMID: 18716619
  291. Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage.
    Cell. 2004 Nov 24;119(5):603-14 PMID: 15550243
  292. Lcd1p recruits Mec1p to DNA lesions in vitro and in vivo.
    Mol Cell. 2002 Apr;9(4):857-69 PMID: 11983176
  293. Role of Dnl4-Lif1 in nonhomologous end-joining repair complex assembly and suppression of homologous recombination.
    Nat Struct Mol Biol. 2007 Jul;14(7):639-46 PMID: 17589524
  294. Poly(ADP-ribose) synthesis in vitro programmed by damaged DNA. A comparison of DNA molecules containing different types of strand breaks.
    J Biol Chem. 1980 Nov 10;255(21):10502-8 PMID: 6253477
  295. 53BP1: function and mechanisms of focal recruitment.
    Biochem Soc Trans. 2009 Aug;37(Pt 4):897-904 PMID: 19614615
  296. DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics.
    Mol Cell Biol. 2007 Oct;27(20):7028-40 PMID: 17709392
  297. Spreading of mammalian DNA-damage response factors studied by ChIP-chip at damaged telomeres.
    EMBO J. 2007 Jun 6;26(11):2707-18 PMID: 17491589
  298. 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility.
    Nature. 2008 Nov 27;456(7221):524-8 PMID: 18931659
  299. Colocalization of multiple DNA double-strand breaks at a single Rad52 repair centre.
    Nat Cell Biol. 2003 Jun;5(6):572-7 PMID: 12766777
  300. BMI1-mediated histone ubiquitylation promotes DNA double-strand break repair.
    J Cell Biol. 2010 Oct 4;191(1):45-60 PMID: 20921134
  301. The ubiquitin landscape at DNA double-strand breaks.
    J Cell Biol. 2009 Nov 2;187(3):319-26 PMID: 19948475
  302. Human Rvb1/Tip49 is required for the histone acetyltransferase activity of Tip60/NuA4 and for the downregulation of phosphorylation on H2AX after DNA damage.
    Mol Cell Biol. 2008 Apr;28(8):2690-700 PMID: 18285460
  303. Human CtIP mediates cell cycle control of DNA end resection and double strand break repair.
    J Biol Chem. 2009 Apr 3;284(14):9558-65 PMID: 19202191
  304. A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint.
    PLoS Biol. 2010 Jan 26;8(1):e1000287 PMID: 20126263
  305. Dephosphorylation of gamma H2A by Glc7/protein phosphatase 1 promotes recovery from inhibition of DNA replication.
    Mol Cell Biol. 2010 Jan;30(1):131-45 PMID: 19884341
  306. Interaction of Ku protein and DNA-dependent protein kinase catalytic subunit with nucleic acids.
    Nucleic Acids Res. 1998 Apr 1;26(7):1551-9 PMID: 9512523
  307. Activation of the cellular DNA damage response in the absence of DNA lesions.
    Science. 2008 Jun 13;320(5882):1507-10 PMID: 18483401
  308. DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain.
    Mol Cell. 2004 Dec 22;16(6):991-1002 PMID: 15610741
  309. ATR and ATRIP: partners in checkpoint signaling.
    Science. 2001 Nov 23;294(5547):1713-6 PMID: 11721054
  310. Human ISWI chromatin-remodeling complexes sample nucleosomes via transient binding reactions and become immobilized at active sites.
    Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19873-8 PMID: 20974961
  311. The DNA-dependent protein kinase interacts with DNA to form a protein-DNA complex that is disrupted by phosphorylation.
    Biochemistry. 2002 Oct 22;41(42):12706-14 PMID: 12379113
  312. Crystal structure of the nucleosome core particle at 2.8 A resolution.
    Nature. 1997 Sep 18;389(6648):251-60 PMID: 9305837
  313. DNA repair in mammalian cells: DNA double-strand break repair: how to fix a broken relationship.
    Cell Mol Life Sci. 2009 Mar;66(6):1039-56 PMID: 19153654
  314. SUMO modification of human XRCC4 regulates its localization and function in DNA double-strand break repair.
    Mol Cell Biol. 2006 Mar;26(5):1786-94 PMID: 16478998
  315. DNA damage foci in mitosis are devoid of 53BP1.
    Cell Cycle. 2009 Oct 15;8(20):3379-83 PMID: 19806024
  316. Colocalization of sensors is sufficient to activate the DNA damage checkpoint in the absence of damage.
    Mol Cell. 2008 May 9;30(3):267-76 PMID: 18471973
  317. Systematic identification of fragile sites via genome-wide location analysis of gamma-H2AX.
    Nat Struct Mol Biol. 2010 Mar;17(3):299-305 PMID: 20139982
  318. PTIP regulates 53BP1 and SMC1 at the DNA damage sites.
    J Biol Chem. 2009 Jul 3;284(27):18078-84 PMID: 19414588
  319. Purified human BRCA2 stimulates RAD51-mediated recombination.
    Nature. 2010 Oct 7;467(7316):678-83 PMID: 20729832
  320. Recruitment of Saccharomyces cerevisiae Dnl4-Lif1 complex to a double-strand break requires interactions with Yku80 and the Xrs2 FHA domain.
    Genetics. 2008 Dec;180(4):1809-19 PMID: 18832348
  321. BRCT repeats as phosphopeptide-binding modules involved in protein targeting.
    Science. 2003 Oct 24;302(5645):636-9 PMID: 14576432
  322. Genetic manipulation of genomes with rare-cutting endonucleases.
    Trends Genet. 1996 Jun;12(6):224-8 PMID: 8928227
  323. The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage.
    J Cell Biol. 2010 Sep 6;190(5):731-40 PMID: 20805324
  324. Mechanisms of chromosomal rearrangement in the human genome.
    BMC Genomics. 2010 Feb 10;11 Suppl 1:S1 PMID: 20158866
  325. Mobilization and recruitment of HP1: a bimodal response to DNA breakage.
    Cell Cycle. 2009 Sep 15;8(18):2945-50 PMID: 19657222
  326. A supramodular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA damage.
    Cell. 2009 Oct 2;139(1):100-11 PMID: 19804756
  327. BRCT domain interactions with phospho-histone H2A target Crb2 to chromatin at double-strand breaks and maintain the DNA damage checkpoint.
    Mol Cell Biol. 2010 Oct;30(19):4732-43 PMID: 20679485
  328. Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions.
    Nature. 2009 Apr 2;458(7238):591-6 PMID: 19234442
  329. The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress.
    Nature. 2009 Dec 17;462(7275):886-90 PMID: 20016594
  330. Nuclear foci of mammalian Rad51 recombination protein in somatic cells after DNA damage and its localization in synaptonemal complexes.
    Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2298-302 PMID: 7892263
  331. The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets.
    Mol Cell. 2010 Jul 9;39(1):8-24 PMID: 20603072
  332. BRIT1/MCPH1 links chromatin remodelling to DNA damage response.
    Nat Cell Biol. 2009 Jul;11(7):865-72 PMID: 19525936
  333. DNA resection in eukaryotes: deciding how to fix the break.
    Nat Struct Mol Biol. 2010 Jan;17(1):11-6 PMID: 20051983
  334. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage.
    Cell. 2009 Feb 6;136(3):420-34 PMID: 19203578
  335. Poly(ADP-ribose) polymerase: a molecular nick-sensor.
    Trends Biochem Sci. 1994 Apr;19(4):172-6 PMID: 8016868
  336. Rad3 decorates critical chromosomal domains with gammaH2A to protect genome integrity during S-Phase in fission yeast.
    PLoS Genet. 2010 Jul 22;6(7):e1001032 PMID: 20661445
  337. 14-3-3 proteins, FHA domains and BRCT domains in the DNA damage response.
    DNA Repair (Amst). 2009 Sep 2;8(9):1009-17 PMID: 19481982
  338. Megabase chromatin domains involved in DNA double-strand breaks in vivo.
    J Cell Biol. 1999 Sep 6;146(5):905-16 PMID: 10477747
  339. ATM phosphorylates histone H2AX in response to DNA double-strand breaks.
    J Biol Chem. 2001 Nov 9;276(45):42462-7 PMID: 11571274
  340. Protein phosphatase 6 interacts with the DNA-dependent protein kinase catalytic subunit and dephosphorylates gamma-H2AX.
    Mol Cell Biol. 2010 Mar;30(6):1368-81 PMID: 20065038
  341. Solution structures of the two PBZ domains from human APLF and their interaction with poly(ADP-ribose).
    Nat Struct Mol Biol. 2010 Feb;17(2):241-3 PMID: 20098424
  342. Lif1p targets the DNA ligase Lig4p to sites of DNA double-strand breaks.
    Curr Biol. 2000 Feb 10;10(3):165-8 PMID: 10679327
  343. Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks.
    Nature. 2009 Dec 17;462(7275):935-9 PMID: 20016603
  344. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139.
    J Biol Chem. 1998 Mar 6;273(10):5858-68 PMID: 9488723
  345. ATM-related Tel1 associates with double-strand breaks through an Xrs2-dependent mechanism.
    Genes Dev. 2003 Aug 15;17(16):1957-62 PMID: 12923051
  346. The Yku70-Yku80 complex contributes to regulate double-strand break processing and checkpoint activation during the cell cycle.
    EMBO Rep. 2008 Aug;9(8):810-8 PMID: 18600234
  347. MOF and histone H4 acetylation at lysine 16 are critical for DNA damage response and double-strand break repair.
    Mol Cell Biol. 2010 Jul;30(14):3582-95 PMID: 20479123
  348. The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation.
    J Biol Chem. 2001 May 4;276(18):14537-40 PMID: 11278247
  349. Histone H2AX stabilizes broken DNA strands to suppress chromosome breaks and translocations during V(D)J recombination.
    J Exp Med. 2009 Nov 23;206(12):2625-39 PMID: 19887394
  350. Non-canonical inhibition of DNA damage-dependent ubiquitination by OTUB1.
    Nature. 2010 Aug 19;466(7309):941-6 PMID: 20725033
  351. BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response.
    Mol Cell. 2009 Oct 9;36(1):110-20 PMID: 19818714
  352. A new method for introducing double-strand breaks into cellular DNA.
    Radiat Res. 1993 May;134(2):160-9 PMID: 7683818
  353. A DNA damage checkpoint response in telomere-initiated senescence.
    Nature. 2003 Nov 13;426(6963):194-8 PMID: 14608368
  354. MRN and the race to the break.
    Chromosoma. 2010 Apr;119(2):115-35 PMID: 19862546
  355. The RecQ DNA helicases in DNA repair.
    Annu Rev Genet. 2010;44:393-417 PMID: 21047263
  356. Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-H2AX and suppresses DNA double strand break repair.
    J Biol Chem. 2010 Apr 23;285(17):12935-47 PMID: 20118229
  357. DNA damage signaling in response to double-strand breaks during mitosis.
    J Cell Biol. 2010 Jul 26;190(2):197-207 PMID: 20660628
  358. Recruitment of heterochromatin protein 1 to DNA repair sites.
    Cytometry A. 2009 Jul;75(7):619-25 PMID: 19479850
  359. The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen.
    Cell. 1993 Jan 15;72(1):131-42 PMID: 8422676
  360. MRE11-RAD50-NBS1 complex dictates DNA repair independent of H2AX.
    J Biol Chem. 2010 Jan 8;285(2):1097-104 PMID: 19910469
  361. Distinct roles for SWR1 and INO80 chromatin remodeling complexes at chromosomal double-strand breaks.
    EMBO J. 2007 Sep 19;26(18):4113-25 PMID: 17762868
  362. DNA methylation and cancer.
    Adv Genet. 2010;70:27-56 PMID: 20920744
  363. Forkhead-associated domain of yeast Xrs2, a homolog of human Nbs1, promotes nonhomologous end joining through interaction with a ligase IV partner protein, Lif1.
    Genetics. 2008 May;179(1):213-25 PMID: 18458108
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.2021311
Published
2011-03-01
Pages
409-33
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC3049283
Subset
IM
Grants
Wellcome Trust · United Kingdom
Cancer Research UK · 11224 · United Kingdom
Cancer Research UK · A11224 · United Kingdom
Biotechnology and Biological Sciences Research Council · United Kingdom
External Links
PubMed source DOI: 10.1101/gad.2021311 PMC Full Text View journal details
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