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PMID: 18541289 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

The role of Cockayne Syndrome group B (CSB) protein in base excision repair and aging.

Mechanisms of ageing and development ·Vol. 129 ·No. 7-8 ·2008-00-00 ·Pages 441-8

Stevnsner T, Muftuoglu M, Aamann MD, Bohr VA

Abstract

Cockayne Syndrome (CS) is a rare human genetic disorder characterized by progressive multisystem degeneration and segmental premature aging. The CS complementation group B (CSB) protein is engaged in transcription coupled and global nucleotide excision repair, base excision repair and general transcription. However, the precise molecular function of the CSB protein is still unclear. In the current review we discuss the involvement of CSB in some of these processes, with focus on the role of CSB in repair of oxidative damage, as deficiencies in the repair of these lesions may be an important aspect of the premature aging phenotype of CS.

MeSH Terms
Aging/genetics Aging, Premature Chromatin/chemistry Cockayne Syndrome/genetics DNA Damage DNA Helicases/genetics,physiology DNA Repair DNA Repair Enzymes/genetics,physiology Humans Poly-ADP-Ribose Binding Proteins
Chemicals
Chromatin Poly-ADP-Ribose Binding Proteins DNA Helicases ERCC6 protein, human DNA Repair Enzymes
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Stevnsner Tinna
Danish Centre for Molecular Gerontology, Department of Molecular Biology, University of Aarhus, C.F. Møllers Allé, Aarhus C, Denmark. [email protected]
Muftuoglu Meltem
Aamann Maria Diget
Bohr Vilhelm A
References (85)
85 references, click to expand
  1. Mitochondrial decay in aging.
    Biochim Biophys Acta. 1995 May 24;1271(1):165-70 PMID: 7599204
  2. Reduced RNA polymerase II transcription in intact and permeabilized Cockayne syndrome group B cells.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4306-11 PMID: 9113985
  3. Transcription through 8-oxoguanine in DNA repair-proficient and Csb(-)/Ogg1(-) DNA repair-deficient mouse embryonic fibroblasts is dependent upon promoter strength and sequence context.
    Mutagenesis. 2007 Sep;22(5):343-51 PMID: 17630408
  4. Effect of 8-oxoguanine on transcription elongation by T7 RNA polymerase and mammalian RNA polymerase II.
    DNA Repair (Amst). 2004 May 4;3(5):483-94 PMID: 15084310
  5. The oxidative DNA lesion 8,5'-(S)-cyclo-2'-deoxyadenosine is repaired by the nucleotide excision repair pathway and blocks gene expression in mammalian cells.
    J Biol Chem. 2000 Jul 21;275(29):22355-62 PMID: 10801836
  6. Human transcription-repair coupling factor CSB/ERCC6 is a DNA-stimulated ATPase but is not a helicase and does not disrupt the ternary transcription complex of stalled RNA polymerase II.
    J Biol Chem. 1997 Jan 17;272(3):1885-90 PMID: 8999876
  7. Role of the ATPase domain of the Cockayne syndrome group B protein in UV induced apoptosis.
    Oncogene. 2000 Jan 27;19(4):477-89 PMID: 10698517
  8. Mitochondrial biology, degenerative diseases and aging.
    Biofactors. 1998;7(3):187-90 PMID: 9568243
  9. A variant of the Cockayne syndrome B gene ERCC6 confers risk of lung cancer.
    Hum Mutat. 2008 Jan;29(1):113-22 PMID: 17854076
  10. Primary fibroblasts of Cockayne syndrome patients are defective in cellular repair of 8-hydroxyguanine and 8-hydroxyadenine resulting from oxidative stress.
    FASEB J. 2003 Apr;17(6):668-74 PMID: 12665480
  11. Fate of RNA polymerase II stalled at a cisplatin lesion.
    J Biol Chem. 2004 Feb 27;279(9):7751-9 PMID: 14672951
  12. Evolution of the SNF2 family of proteins: subfamilies with distinct sequences and functions.
    Nucleic Acids Res. 1995 Jul 25;23(14):2715-23 PMID: 7651832
  13. Methylating agents and DNA repair responses: Methylated bases and sources of strand breaks.
    Chem Res Toxicol. 2006 Dec;19(12):1580-94 PMID: 17173371
  14. Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer predisposition.
    Cell. 1997 May 2;89(3):425-35 PMID: 9150142
  15. Age-related loss of the DNA repair response following exposure to oxidative stress.
    J Gerontol A Biol Sci Med Sci. 2006 May;61(5):427-34 PMID: 16720738
  16. The transcriptional response after oxidative stress is defective in Cockayne syndrome group B cells.
    Oncogene. 2003 Feb 27;22(8):1135-49 PMID: 12606941
  17. Cell type-specific hypersensitivity to oxidative damage in CSB and XPA mice.
    DNA Repair (Amst). 2003 Jan 2;2(1):13-25 PMID: 12509265
  18. Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects.
    Cell Res. 2008 Jan;18(1):73-84 PMID: 18166977
  19. RNA polymerase II stalled at a thymine dimer: footprint and effect on excision repair.
    Nucleic Acids Res. 1997 Feb 15;25(4):787-93 PMID: 9016630
  20. Effects of DNA damaging agents on cultured fibroblasts derived from patients with Cockayne syndrome.
    Mutat Res. 1979 Jan;59(1):49-60 PMID: 431551
  21. Disruption of the Cockayne syndrome B gene impairs spontaneous tumorigenesis in cancer-predisposed Ink4a/ARF knockout mice.
    Mol Cell Biol. 2001 Mar;21(5):1810-8 PMID: 11238917
  22. Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death.
    Mutat Res. 2001 Jun 2;477(1-2):97-110 PMID: 11376691
  23. Nucleotide excision repair disorders and the balance between cancer and aging.
    Cell Cycle. 2006 Dec;5(24):2886-8 PMID: 17172862
  24. Poly(ADP-ribosyl)ation accelerates DNA repair in a pathway dependent on Cockayne syndrome B protein.
    Nucleic Acids Res. 2003 Sep 15;31(18):5332-7 PMID: 12954769
  25. Phenotypic consequences of mutations in the conserved motifs of the putative helicase domain of the human Cockayne syndrome group B gene.
    Gene. 2002 Jan 23;283(1-2):27-40 PMID: 11867210
  26. Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome.
    Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15410-5 PMID: 15486090
  27. Activation of RNA polymerase I transcription by cockayne syndrome group B protein and histone methyltransferase G9a.
    Mol Cell. 2007 Aug 17;27(4):585-95 PMID: 17707230
  28. Paraquat induced DNA damage by reactive oxygen species.
    Biochem Mol Biol Int. 1996 May;39(1):63-7 PMID: 8799328
  29. Cockayne syndrome protein B interacts with and is phosphorylated by c-Abl tyrosine kinase.
    Nucleic Acids Res. 2007;35(15):4941-51 PMID: 17626041
  30. Recruitment of the putative transcription-repair coupling factor CSB/ERCC6 to RNA polymerase II elongation complexes.
    Mol Cell Biol. 1997 Dec;17(12):6803-14 PMID: 9372911
  31. Mammalian 8-oxoguanine DNA glycosylase 1 incises 8-oxoadenine opposite cytosine in nuclei and mitochondria, while a different glycosylase incises 8-oxoadenine opposite guanine in nuclei.
    J Biol Chem. 2003 May 23;278(21):19541-8 PMID: 12644468
  32. Cockayne syndrome group B cellular and biochemical functions.
    Am J Hum Genet. 2003 Dec;73(6):1217-39 PMID: 14639525
  33. The CSB protein actively wraps DNA.
    J Biol Chem. 2005 Feb 11;280(6):4722-9 PMID: 15548521
  34. The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH.
    Cell. 1995 Aug 25;82(4):555-64 PMID: 7664335
  35. Three unusual repair deficiencies associated with transcription factor BTF2(TFIIH): evidence for the existence of a transcription syndrome.
    Cold Spring Harb Symp Quant Biol. 1994;59:317-29 PMID: 7587084
  36. Changes in DNA repair during aging.
    Nucleic Acids Res. 2007;35(22):7466-74 PMID: 17913742
  37. Different effects of CSA and CSB deficiency on sensitivity to oxidative DNA damage.
    Mol Cell Biol. 2004 Sep;24(18):7941-8 PMID: 15340056
  38. The case for 8,5'-cyclopurine-2'-deoxynucleosides as endogenous DNA lesions that cause neurodegeneration in xeroderma pigmentosum.
    Neuroscience. 2007 Apr 14;145(4):1407-17 PMID: 17184928
  39. ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor.
    Mol Cell Biol. 2000 Oct;20(20):7643-53 PMID: 11003660
  40. Functional consequences of mutations in the conserved SF2 motifs and post-translational phosphorylation of the CSB protein.
    Nucleic Acids Res. 2003 Feb 1;31(3):963-73 PMID: 12560492
  41. Cockayne syndrome B protein stimulates apurinic endonuclease 1 activity and protects against agents that introduce base excision repair intermediates.
    Nucleic Acids Res. 2007;35(12):4103-13 PMID: 17567611
  42. SWI2/SNF2 and related proteins: ATP-driven motors that disrupt protein-DNA interactions?
    Cell. 1997 Mar 21;88(6):737-40 PMID: 9118215
  43. Molecular analysis of mutations in the CSB (ERCC6) gene in patients with Cockayne syndrome.
    Am J Hum Genet. 1998 Jan;62(1):77-85 PMID: 9443879
  44. Single-stranded breaks in DNA but not oxidative DNA base damages block transcriptional elongation by RNA polymerase II in HeLa cell nuclear extracts.
    J Biol Chem. 2004 Apr 30;279(18):18511-20 PMID: 14978042
  45. A global DNA repair mechanism involving the Cockayne syndrome B (CSB) gene product can prevent the in vivo accumulation of endogenous oxidative DNA base damage.
    Oncogene. 2002 Nov 28;21(54):8232-9 PMID: 12447686
  46. Localization of the nucleotide excision repair gene ERCC6 to human chromosome 10q11-q21.
    Genomics. 1992 Apr;12(4):745-9 PMID: 1349298
  47. Preferential repair of ionizing radiation-induced damage in the transcribed strand of an active human gene is defective in Cockayne syndrome.
    Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10499-503 PMID: 8248136
  48. Initiation of DNA repair mediated by a stalled RNA polymerase IIO.
    EMBO J. 2006 Jan 25;25(2):387-97 PMID: 16407975
  49. Complementation of the oxidatively damaged DNA repair defect in Cockayne syndrome A and B cells by Escherichia coli formamidopyrimidine DNA glycosylase.
    Free Radic Biol Med. 2007 Jun 15;42(12):1807-17 PMID: 17512460
  50. Gene expression and DNA repair in progeroid syndromes and human aging.
    Ageing Res Rev. 2005 Nov;4(4):579-602 PMID: 16246641
  51. Retinal degeneration and ionizing radiation hypersensitivity in a mouse model for Cockayne syndrome.
    Mol Cell Biol. 2007 Feb;27(4):1433-41 PMID: 17145777
  52. Cockayne syndrome group B protein enhances elongation by RNA polymerase II.
    Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11205-9 PMID: 9326587
  53. Alterations in the CSB gene in three Italian patients with the severe form of Cockayne syndrome (CS) but without clinical photosensitivity.
    Hum Mol Genet. 1999 May;8(5):935-41 PMID: 10196384
  54. Reduced RNA polymerase II transcription in extracts of cockayne syndrome and xeroderma pigmentosum/Cockayne syndrome cells.
    Nucleic Acids Res. 1997 Sep 15;25(18):3636-42 PMID: 9278484
  55. Mitochondrial and nuclear DNA-repair capacity of various brain regions in mouse is altered in an age-dependent manner.
    Neurobiol Aging. 2006 Aug;27(8):1129-36 PMID: 16005114
  56. Cockayne syndrome: review of 140 cases.
    Am J Med Genet. 1992 Jan 1;42(1):68-84 PMID: 1308368
  57. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage.
    Cell. 2003 May 2;113(3):357-67 PMID: 12732143
  58. Structural characterization of RNA polymerase II complexes arrested by a cyclobutane pyrimidine dimer in the transcribed strand of template DNA.
    J Biol Chem. 1999 Aug 20;274(34):24124-30 PMID: 10446184
  59. The Cockayne Syndrome group B gene product is involved in general genome base excision repair of 8-hydroxyguanine in DNA.
    J Biol Chem. 2001 Dec 7;276(49):45772-9 PMID: 11581270
  60. Repair of 8-oxoguanine in DNA is deficient in Cockayne syndrome group B cells.
    Nucleic Acids Res. 1999 Mar 1;27(5):1365-8 PMID: 9973627
  61. ATP-dependent chromatin remodeling factors and DNA damage repair.
    Mutat Res. 2007 May 1;618(1-2):65-80 PMID: 17291544
  62. Transcription activities at 8-oxoG lesions in DNA.
    DNA Repair (Amst). 2004 Nov 2;3(11):1457-68 PMID: 15380101
  63. Potassium bromate but not X-rays cause unexpectedly elevated levels of DNA breakage similar to those induced by ultraviolet light in Cockayne syndrome (CS-B) fibroblasts.
    Cytogenet Genome Res. 2004;104(1-4):178-81 PMID: 15162034
  64. Functional crosstalk between hOgg1 and the helicase domain of Cockayne syndrome group B protein.
    DNA Repair (Amst). 2002 Nov 3;1(11):913-27 PMID: 12531019
  65. ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne's syndrome and preferential repair of active genes.
    Cell. 1992 Dec 11;71(6):939-53 PMID: 1339317
  66. The cockayne syndrome group B gene product is involved in cellular repair of 8-hydroxyadenine in DNA.
    J Biol Chem. 2002 Aug 23;277(34):30832-7 PMID: 12060667
  67. The Cockayne syndrome group B protein is a functional dimer.
    FEBS J. 2005 Sep;272(17):4306-14 PMID: 16128801
  68. Genetic syndromes in man with potential relevance to the pathobiology of aging.
    Birth Defects Orig Artic Ser. 1978;14(1):5-39 PMID: 147113
  69. The Cockayne syndrome B protein, involved in transcription-coupled DNA repair, resides in an RNA polymerase II-containing complex.
    EMBO J. 1997 Oct 1;16(19):5955-65 PMID: 9312053
  70. Deletion of 5' sequences of the CSB gene provides insight into the pathophysiology of Cockayne syndrome.
    Eur J Hum Genet. 2008 Mar;16(3):320-7 PMID: 18183039
  71. ATP-dependent chromatin remodeling is required for base excision repair in conventional but not in variant H2A.Bbd nucleosomes.
    Mol Cell Biol. 2007 Sep;27(17):5949-56 PMID: 17591702
  72. Cockayne syndrome group B protein has novel strand annealing and exchange activities.
    Nucleic Acids Res. 2006 Jan 12;34(1):295-304 PMID: 16410611
  73. siRNA-mediated silencing of Cockayne Cyndrome group B gene potentiates radiation-induced apoptosis and antiproliferative effect in HeLa cells.
    Chin Med J (Engl). 2006 May 5;119(9):731-9 PMID: 16701013
  74. The genetic defect in Cockayne syndrome is associated with a defect in repair of UV-induced DNA damage in transcriptionally active DNA.
    Proc Natl Acad Sci U S A. 1990 Jun;87(12):4707-11 PMID: 2352945
  75. Molecular characterization of an acidic region deletion mutant of Cockayne syndrome group B protein.
    Nucleic Acids Res. 2000 Aug 15;28(16):3151-9 PMID: 10931931
  76. Increased apoptosis, p53 up-regulation, and cerebellar neuronal degeneration in repair-deficient Cockayne syndrome mice.
    Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1389-94 PMID: 17229834
  77. Cockayne syndrome B protein regulates the transcriptional program after UV irradiation.
    EMBO J. 2006 May 3;25(9):1915-23 PMID: 16601682
  78. Neurodegeneration in hereditary nucleotide repair disorders.
    Brain Dev. 1999 Jul;21(5):326-33 PMID: 10413020
  79. When transcription and repair meet: a complex system.
    Trends Genet. 2006 Aug;22(8):430-6 PMID: 16797777
  80. Effects of endogenous DNA base lesions on transcription elongation by mammalian RNA polymerase II. Implications for transcription-coupled DNA repair and transcriptional mutagenesis.
    J Biol Chem. 2003 Feb 28;278(9):7294-9 PMID: 12466278
  81. Cooperation of the Cockayne syndrome group B protein and poly(ADP-ribose) polymerase 1 in the response to oxidative stress.
    Mol Cell Biol. 2005 Sep;25(17):7625-36 PMID: 16107709
  82. Effects of nonbulky DNA base damages on Escherichia coli RNA polymerase-mediated elongation and promoter clearance.
    J Biol Chem. 1998 Aug 14;273(33):21276-81 PMID: 9694887
  83. Mitochondrial repair of 8-oxoguanine is deficient in Cockayne syndrome group B.
    Oncogene. 2002 Dec 12;21(57):8675-82 PMID: 12483520
  84. Cockayne syndrome group B protein (CSB) plays a general role in chromatin maintenance and remodeling.
    Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9613-8 PMID: 16772382
  85. A mammalian cell line deficient in activity of the DNA repair enzyme 5-hydroxymethyluracil-DNA glycosylase is resistant to the toxic effects of the thymidine analog 5-hydroxymethyl-2'-deoxyuridine.
    Mol Cell Biol. 1992 Dec;12(12):5536-40 PMID: 1448084
Article Info
Journal
Mechanisms of ageing and development
Abbr.
Mech Ageing Dev
ISSN
0047-6374
DOI
10.1016/j.mad.2008.04.009
Email
[email protected]
Published
2008-00-00
Epub
2008-00-30
Pages
441-8
Language
English
Region
Ireland
NLM ID
0347227
PMCID
PMC2538557
Subset
IM
Grants
Intramural NIH HHS · Z01 AG000726-15 · United States
Intramural NIH HHS · Z01 AG000727-15 · United States
External Links
PubMed source DOI: 10.1016/j.mad.2008.04.009 PMC Full Text View journal details
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