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PMID: 17923688 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Requirement of Nse1, a subunit of the Smc5-Smc6 complex, for Rad52-dependent postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae.

Molecular and cellular biology ·Vol. 27 ·No. 23 ·2007-12-00 ·Pages 8409-18

Santa Maria SR, Gangavarapu V, Johnson RE, Prakash L, Prakash S

Abstract

In Saccharomyces cerevisiae, postreplication repair (PRR) of UV-damaged DNA occurs by a Rad6-Rad18- and an Mms2-Ubc13-Rad5-dependent pathway or by a Rad52-dependent pathway. The Rad5 DNA helicase activity is specialized for promoting replication fork regression and template switching; previously, we suggested a role for the Rad5-dependent PRR pathway when the lesion is located on the leading strand and a role for the Rad52 pathway when the lesion is located on the lagging strand. In this study, we present evidence for the requirement of Nse1, a subunit of the Smc5-Smc6 complex, in Rad52-dependent PRR, and our genetic analyses suggest a role for the Nse1 and Mms21 E3 ligase activities associated with this complex in this repair mode. We discuss the possible ways by which the Smc5-Smc6 complex, including its associated ubiquitin ligase and SUMO ligase activities, might contribute to the Rad52-dependent nonrecombinational and recombinational modes of PRR.

MeSH Terms
Amino Acid Motifs Amino Acid Sequence Cell Cycle Proteins/metabolism DNA Damage DNA Repair/radiation effects DNA Replication/radiation effects DNA, Fungal/metabolism Epistasis, Genetic Molecular Sequence Data Mutant Proteins/isolation & purification,metabolism Mutation/genetics Nuclear Proteins/chemistry,metabolism Proliferating Cell Nuclear Antigen/metabolism Protein Subunits/metabolism Rad52 DNA Repair and Recombination Protein/metabolism SUMO-1 Protein/metabolism Saccharomyces cerevisiae/cytology,enzymology,radiation effects Saccharomyces cerevisiae Proteins/chemistry,metabolism Ubiquitin-Protein Ligases/metabolism Ultraviolet Rays
Chemicals
Cell Cycle Proteins DNA, Fungal Mms21 protein, S cerevisiae Mutant Proteins NSE1 protein, S cerevisiae Nuclear Proteins Proliferating Cell Nuclear Antigen Protein Subunits RAD52 protein, S cerevisiae Rad52 DNA Repair and Recombination Protein SMC5 protein, S cerevisiae SMC6 protein, S cerevisiae SUMO-1 Protein Saccharomyces cerevisiae Proteins Ubiquitin-Protein Ligases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Santa Maria Sergio R
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 301 University Blvd., Galveston, TX 77555-1061, USA.
Gangavarapu Venkateswarlu
Johnson Robert E
Prakash Louise
Prakash Satya
References (50)
50 references, click to expand
  1. Dynamic molecular linkers of the genome: the first decade of SMC proteins.
    Genes Dev. 2005 Jun 1;19(11):1269-87 PMID: 15937217
  2. Requirement of yeast SGS1 and SRS2 genes for replication and transcription.
    Science. 1999 Dec 17;286(5448):2339-42 PMID: 10600744
  3. Identification of a novel non-structural maintenance of chromosomes (SMC) component of the SMC5-SMC6 complex involved in DNA repair.
    J Biol Chem. 2002 Jun 14;277(24):21585-91 PMID: 11927594
  4. 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
  5. Assigning function to yeast proteins by integration of technologies.
    Mol Cell. 2003 Dec;12(6):1353-65 PMID: 14690591
  6. Characterization of postreplication repair in Saccharomyces cerevisiae and effects of rad6, rad18, rev3 and rad52 mutations.
    Mol Gen Genet. 1981;184(3):471-8 PMID: 7038396
  7. Fidelity of human DNA polymerase eta.
    J Biol Chem. 2000 Mar 17;275(11):7447-50 PMID: 10713043
  8. Requirement of RAD52 group genes for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae.
    Mol Cell Biol. 2007 Nov;27(21):7758-64 PMID: 17785441
  9. Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function.
    Annu Rev Biochem. 2005;74:317-53 PMID: 15952890
  10. Molecular architecture of SMC proteins and the yeast cohesin complex.
    Mol Cell. 2002 Apr;9(4):773-88 PMID: 11983169
  11. Requirement of proliferating cell nuclear antigen in RAD6-dependent postreplicational DNA repair.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9676-81 PMID: 8790390
  12. Mms2-Ubc13-dependent and -independent roles of Rad5 ubiquitin ligase in postreplication repair and translesion DNA synthesis in Saccharomyces cerevisiae.
    Mol Cell Biol. 2006 Oct;26(20):7783-90 PMID: 16908531
  13. Qri2/Nse4, a component of the essential Smc5/6 DNA repair complex.
    Mol Microbiol. 2005 Mar;55(6):1735-50 PMID: 15752197
  14. Isolation and characterization of MMS-sensitive mutants of Saccharomyces cerevisiae.
    Genetics. 1977 May;86(1):33-55 PMID: 195865
  15. Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Poleta.
    Science. 1999 Feb 12;283(5404):1001-4 PMID: 9974380
  16. Mechanism of homologous recombination: mediators and helicases take on regulatory functions.
    Nat Rev Mol Cell Biol. 2006 Oct;7(10):739-50 PMID: 16926856
  17. Increased spontaneous mitotic segregation in MMS-sensitive mutants of Saccharomyces cerevisiae.
    Genetics. 1977 Oct;87(2):229-36 PMID: 200524
  18. Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5-Smc6 complex.
    J Biol Chem. 2003 Nov 14;278(46):45460-7 PMID: 12966087
  19. Mechanism of nucleotide incorporation opposite a thymine-thymine dimer by yeast DNA polymerase eta.
    Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12093-8 PMID: 14527996
  20. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair.
    Cell. 1999 Mar 5;96(5):645-53 PMID: 10089880
  21. Analysis of DNA replication forks encountering a pyrimidine dimer in the template to the leading strand.
    J Mol Biol. 1999 Jun 25;289(5):1207-18 PMID: 10373362
  22. Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases.
    Nat Genet. 2000 Jun;25(2):192-4 PMID: 10835635
  23. A novel SMC protein complex in Schizosaccharomyces pombe contains the Rad18 DNA repair protein.
    EMBO J. 2000 Apr 3;19(7):1691-702 PMID: 10747036
  24. The many functions of SMC proteins in chromosome dynamics.
    Nat Rev Mol Cell Biol. 2002 Oct;3(10):767-78 PMID: 12360193
  25. Differential replication of a single, UV-induced lesion in the leading or lagging strand by a human cell extract: fork uncoupling or gap formation.
    Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):11975-9 PMID: 8618826
  26. SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase.
    Nature. 2005 Jul 21;436(7049):428-33 PMID: 15931174
  27. The rad18 gene of Schizosaccharomyces pombe defines a new subgroup of the SMC superfamily involved in DNA repair.
    Mol Cell Biol. 1995 Dec;15(12):7067-80 PMID: 8524274
  28. Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has ubiquitin conjugating, DNA binding, and ATP hydrolytic activities.
    J Biol Chem. 1997 Sep 12;272(37):23360-5 PMID: 9287349
  29. Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions.
    Mol Cell. 2006 Jan 6;21(1):15-27 PMID: 16387650
  30. Saccharomyces cerevisiae RAD5-encoded DNA repair protein contains DNA helicase and zinc-binding sequence motifs and affects the stability of simple repetitive sequences in the genome.
    Mol Cell Biol. 1992 Sep;12(9):3807-18 PMID: 1324406
  31. Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p.
    Mol Cell. 2005 Jul 1;19(1):123-33 PMID: 15989970
  32. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO.
    Nature. 2002 Sep 12;419(6903):135-41 PMID: 12226657
  33. Opposing effects of ubiquitin conjugation and SUMO modification of PCNA on replicational bypass of DNA lesions in Saccharomyces cerevisiae.
    Mol Cell Biol. 2004 May;24(10):4267-74 PMID: 15121847
  34. Rad18 is required for DNA repair and checkpoint responses in fission yeast.
    Mol Biol Cell. 1999 Sep;10(9):2905-18 PMID: 10473635
  35. Replication fork bypass of a pyrimidine dimer blocking leading strand DNA synthesis.
    J Biol Chem. 1997 May 23;272(21):13945-54 PMID: 9153257
  36. A topological interaction between cohesin rings and a circular minichromosome.
    Cell. 2005 Sep 23;122(6):849-60 PMID: 16179255
  37. The SRS2 suppressor of rad6 mutations of Saccharomyces cerevisiae acts by channeling DNA lesions into the RAD52 DNA repair pathway.
    Genetics. 1990 Apr;124(4):817-31 PMID: 2182387
  38. Nse2, a component of the Smc5-6 complex, is a SUMO ligase required for the response to DNA damage.
    Mol Cell Biol. 2005 Jan;25(1):185-96 PMID: 15601841
  39. Role of DNA polymerase eta in the bypass of a (6-4) TT photoproduct.
    Mol Cell Biol. 2001 May;21(10):3558-63 PMID: 11313481
  40. Recombination proteins in yeast.
    Annu Rev Genet. 2004;38:233-71 PMID: 15568977
  41. Yeast Rad5 protein required for postreplication repair has a DNA helicase activity specific for replication fork regression.
    Mol Cell. 2007 Oct 12;28(1):167-75 PMID: 17936713
  42. Specific complex formation between yeast RAD6 and RAD18 proteins: a potential mechanism for targeting RAD6 ubiquitin-conjugating activity to DNA damage sites.
    Genes Dev. 1994 Apr 1;8(7):811-20 PMID: 7926769
  43. Eukaryotic polymerases iota and zeta act sequentially to bypass DNA lesions.
    Nature. 2000 Aug 31;406(6799):1015-9 PMID: 10984059
  44. Accuracy of thymine-thymine dimer bypass by Saccharomyces cerevisiae DNA polymerase eta.
    Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3094-9 PMID: 10725365
  45. Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair.
    EMBO J. 2000 Jul 3;19(13):3388-97 PMID: 10880451
  46. Yeast DNA repair protein RAD5 that promotes instability of simple repetitive sequences is a DNA-dependent ATPase.
    J Biol Chem. 1994 Nov 11;269(45):28259-62 PMID: 7961763
  47. Requirement of RAD5 and MMS2 for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae.
    Mol Cell Biol. 2002 Apr;22(7):2419-26 PMID: 11884624
  48. Hyper-recombination and mutator effects of the mms9-1, mms13-1, and mms21-1 mutations in Saccharomyces cerevisiae.
    Curr Genet. 1981 Dec;4(3):223-32 PMID: 24185997
  49. Thymine-thymine dimer bypass by yeast DNA polymerase zeta.
    Science. 1996 Jun 14;272(5268):1646-9 PMID: 8658138
  50. Opening closed arms: long-distance activation of SMC ATPase by hinge-DNA interactions.
    Mol Cell. 2006 Jan 20;21(2):175-86 PMID: 16427008
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
Published
2007-12-00
Epub
2007-00-08
Pages
8409-18
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2169175
Subset
IM
Grants
NCI NIH HHS · R01 CA107650 · United States
NCI NIH HHS · CA107650 · United States
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