Critical Functions of Rpa3/Ssb3 in S-Phase DNA Damage Responses in Fission Yeast

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Replication Protein A (RPA) is a heterotrimeric, single-stranded DNA (ssDNA)–binding complex required for DNA replication and repair, homologous recombination, DNA damage checkpoint signaling, and telomere maintenance. Whilst the larger RPA subunits, Rpa1 and Rpa2, have essential interactions with ssDNA, the molecular functions of the smallest subunit Rpa3 are unknown. Here, we investigate the Rpa3 ortholog Ssb3 in Schizosaccharomyces pombe and find that it is dispensable for cell viability, checkpoint signaling, RPA foci formation, and meiosis. However, increased spontaneous Rad11^Rpa1 and Rad22^Rad52 nuclear foci in ssb3Δ cells indicate genome maintenance defects. Moreover, Ssb3 is required for resistance to genotoxins that disrupt DNA replication. Genetic interaction studies indicate that Ssb3 has a close functional relationship with the Mms1-Mms22 protein complex, which is required for survival after DNA damage in S-phase, and with the mitotic functions of Mus81-Eme1 Holliday junction resolvase that is required for recovery from replication fork collapse. From these studies we propose that Ssb3 plays a critical role in mediating RPA functions that are required for repair or tolerance of DNA lesions in S-phase. Rpa3 orthologs in humans and other species may have a similar function.

Vyšlo v časopise: Critical Functions of Rpa3/Ssb3 in S-Phase DNA Damage Responses in Fission Yeast. PLoS Genet 6(9): e32767. doi:10.1371/journal.pgen.1001138
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001138

Souhrn

Zdroje

1. BinzSK

SheehanAM

WoldMS

2004 Replication protein A phosphorylation and the cellular response to DNA damage. DNA Repair 3 1015 1024

2. RichardDJ

BoldersonE

KhannaKK

2009 Multiple human single-stranded DNA binding proteins function in genome maintenance: structural, biochemical and functional analysis. Crit Rev Biochem Mol Biol 1 19

3. WoldMS

1997 Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism. Annu Rev Biochem 66 61 92

4. IftodeC

DanielyY

BorowiecJA

1999 Replication protein A (RPA): the eukaryotic SSB. Crit Rev Biochem Mol Biol 34 141 180

5. WobbeCR

WeissbachL

BorowiecJA

DeanFB

MurakamiY

1987 Replication of simian virus 40 origin-containing DNA in vitro with purified proteins. Proc Natl Acad Sci U S A 84 1834 1838

6. FairmanMP

StillmanB

1988 Cellular factors required for multiple stages of SV40 DNA replication in vitro. EMBO J 7 1211 1218

7. WoldMS

KellyT

1988 Purification and characterization of replication protein A, a cellular protein required for in vitro replication of simian virus 40 DNA. Proc Natl Acad Sci U S A 85 2523 2527

8. HeZ

HenricksenLA

WoldMS

InglesCJ

1995 RPA involvement in the damage-recognition and incision steps of nucleotide excision repair. Nature 374 566 569

9. LinYL

ShivjiMK

ChenC

KolodnerR

WoodRD

1998 The evolutionarily conserved zinc finger motif in the largest subunit of human replication protein A is required for DNA replication and mismatch repair but not for nucleotide excision repair. J Biol Chem 273 1453 1461

10. Bastin-ShanowerSA

BrillSJ

2001 Functional analysis of the four DNA binding domains of replication protein A. The role of RPA2 in ssDNA binding. J Biol Chem 276 36446 36453

11. BochkarevA

BochkarevaE

2004 From RPA to BRCA2: lessons from single-stranded DNA binding by the OB-fold. Curr Opin Struct Biol 14 36 42

12. HenricksenLA

UmbrichtCB

WoldMS

1994 Recombinant replication protein A: expression, complex formation, and functional characterization. J Biol Chem 269 11121 11132

13. StiggerE

DeanFB

HurwitzJ

LeeSH

1994 Reconstitution of functional human single-stranded DNA-binding protein from individual subunits expressed by recombinant baculoviruses. Proc Natl Acad Sci U S A 91 579 583

14. BrillSJ

StillmanB

1991 Replication factor-A from Saccharomyces cerevisiae is encoded by three essential genes coordinately expressed at S phase. Genes Dev 5 1589 1600

15. ZouL

ElledgeSJ

2003 Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300 1542 1548

16. BallHL

EhrhardtMR

MordesDA

GlickGG

ChazinWJ

2007 Function of a conserved checkpoint recruitment domain in ATRIP proteins. Mol Cell Biol 27 3367 3377

17. ManiarHS

WilsonR

BrillSJ

1997 Roles of replication protein-A subunits 2 and 3 in DNA replication fork movement in Saccharomyces cerevisiae. Genetics 145 891 902

18. PommierY

2006 Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer 6 789 802

19. KosterDA

PalleK

BotES

BjornstiMA

DekkerNH

2007 Antitumour drugs impede DNA uncoiling by topoisomerase I. Nature 448 213 217

20. RoseaulinL

YamadaY

TsutsuiY

RussellP

IwasakiH

2008 Mus81 is essential for sister chromatid recombination at broken replication forks. Embo J 27 1378 1387

21. BoddyMN

GaillardPH

McDonaldWH

ShanahanP

YatesJR3rd

2001 Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell 107 537 548

22. BoddyMN

Lopez-GironaA

ShanahanP

InterthalH

HeyerWD

2000 Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1. Mol Cell Biol 20 8758 8766

23. DoeCL

AhnJS

DixonJ

WhitbyMC

2002 Mus81-Eme1 and Rqh1 involvement in processing stalled and collapsed replication forks. J Biol Chem 277 32753 32759

24. YokoyamaM

InoueH

IshiiC

MurakamiY

2007 The novel gene mus7+ is involved in the repair of replication-associated DNA damage in fission yeast. DNA Repair 6 770 780

25. DoveyCL

RussellP

2007 Mms22 preserves genomic integrity during DNA replication in Schizosaccharomyces pombe. Genetics 177 47 61

26. DuroE

VaisicaJA

BrownGW

RouseJ

2008 Budding yeast Mms22 and Mms1 regulate homologous recombination induced by replisome blockage. DNA Repair 7 811 818

27. ZaidiIW

RabutG

PovedaA

ScheelH

MalmstromJ

2008 Rtt101 and Mms1 in budding yeast form a CUL4(DDB1)-like ubiquitin ligase that promotes replication through damaged DNA. EMBO Rep 9 1034 1040

28. DoveyCL

AslanianA

SofuevaS

YatesJR3rd

RussellP

2009 Mms1-Mms22 complex protects genome integrity in Schizosaccharomyces pombe. DNA Repair 8 1390 1399

29. DeshpandeGP

HaylesJ

HoeKL

KimDU

ParkHO

2009 Screening a genome-wide S. pombe deletion library identifies novel genes and pathways involved in genome stability maintenance. DNA Repair 8 672 679

30. ParkerAE

ClyneRK

CarrAM

KellyTJ

1997 The Schizosaccharomyces pombe rad11+ gene encodes the large subunit of replication protein A. Mol Cell Biol 17 2381 2390

31. SmithGR

BoddyMN

ShanahanP

RussellP

2003 Fission yeast Mus81.Eme1 Holliday junction resolvase is required for meiotic crossing over but not for gene conversion. Genetics 165 2289 2293

32. RhindN

RussellP

2000 Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways. J Cell Sci 113 3889 3896

33. WalworthNC

BernardsR

1996 rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint. Science 271 353 356

34. NoguchiE

NoguchiC

DuLL

RussellP

2003 Swi1 prevents replication fork collapse and controls checkpoint kinase Cds1. Mol Cell Biol 23 7861 7874

35. MeisterP

PoidevinM

FrancesconiS

TratnerI

ZarzovP

2003 Nuclear factories for signalling and repairing DNA double strand breaks in living fission yeast. Nucleic Acids Res 31 5064 5073

36. DuLL

NakamuraTM

MoserBA

RussellP

2003 Retention but not recruitment of Crb2 at double-strand breaks requires Rad1 and Rad3 complexes. Mol Cell Biol 23 6150 6158

37. NoguchiE

NoguchiC

McDonaldWH

YatesJR3rd

RussellP

2004 Swi1 and Swi3 are components of a replication fork protection complex in fission yeast. Mol Cell Biol 24 8342 8355

38. AnsbachAB

NoguchiC

KlansekIW

HeidlebaughM

NakamuraTM

2008 RFCCtf18 and the Swi1-Swi3 complex function in separate and redundant pathways required for the stabilization of replication forks to facilitate sister chromatid cohesion in Schizosaccharomyces pombe. Mol Biol Cell 19 595 607

39. ShimadaM

OkuzakiD

TanakaS

TouganT

TamaiKK

1999 Replication factor C3 of Schizosaccharomyces pombe, a small subunit of replication factor C complex, plays a role in both replication and damage checkpoints. Mol Biol Cell 10 3991 4003

40. KhasanovFK

SavchenkoGV

BashkirovaEV

KorolevVG

HeyerWD

1999 A new recombinational DNA repair gene from Schizosaccharomyces pombe with homology to Escherichia coli RecA. Genetics 152 1557 1572

41. SheedyDM

DimitrovaD

RankinJK

BassKL

LeeKM

2005 Brc1-mediated DNA repair and damage tolerance. Genetics 171 457 468

42. WilliamsJS

WilliamsRS

DoveyCL

GuentherG

TainerJA

2010 gammaH2A binds Brc1 to maintain genome integrity during S-phase. EMBO J 29 1136 1148

43. GaillardPH

NoguchiE

ShanahanP

RussellP

2003 The endogenous Mus81-Eme1 complex resolves Holliday junctions by a nick and counternick mechanism. Mol Cell 12 747 759

44. CromieGA

HyppaRW

TaylorAF

ZakharyevichK

HunterN

2006 Single Holliday junctions are intermediates of meiotic recombination. Cell 127 1167 1178

45. SungP

1997 Yeast Rad55 and Rad57 proteins form a heterodimer that functions with replication protein A to promote DNA strand exchange by Rad51 recombinase. Genes Dev 11 1111 1121

46. AkamatsuY

TsutsuiY

MorishitaT

SiddiqueMS

KurokawaY

2007 Fission yeast Swi5/Sfr1 and Rhp55/Rhp57 differentially regulate Rhp51-dependent recombination outcomes. EMBO J 26 1352 1362

47. KurokawaY

MurayamaY

Haruta-TakahashiN

UrabeI

IwasakiH

2008 Reconstitution of DNA strand exchange mediated by Rhp51 recombinase and two mediators. PLoS Biol 6 e88 doi:10.1371/journal.pbio.0060088