Multiple Regulation of Rad51-Mediated Homologous Recombination by Fission Yeast Fbh1

English version České info

Homologous recombination is required for repairing DNA double-strand breaks (DSBs), which are induced by exogenous factors such as DNA damaging agents or by endogenous factors such as collapse of DNA replication fork in mitotic cells. If improperly processed, DSBs could lead to chromosome rearrangement, cell death, or tumorigenesis in mammals, and thus HR is strictly controlled at several steps, including Rad51 recombinase-driven DNA strand exchange reaction. Specifically, DNA helicases have been shown to be important for suppression of inappropriate recombination events. In this study, we analyzed one such DNA helicase, fission yeast Fbh1. We used an in vivo single-DSB repair assay to show that Fbh1 suppresses crossover formation between homologous chromosomes. Next, we obtained in vitro evidence that Fbh1 acts as an inhibitor of the strand-exchange reaction in the absence of Swi5-Sfr1, but stimulates the reaction after it starts. Furthermore, we found that SCFFbh1 has ubiquitin-ligase activity toward Rad51 in vitro and that Fbh1 regulates the protein level of Rad51 in the stationary phase. These results suggest Fbh1 regulates Rad51-mediated homologous recombination by its seemingly-unrelated two activities, DNA helicase/translocase and ubiquitin ligase.

Vyšlo v časopise: Multiple Regulation of Rad51-Mediated Homologous Recombination by Fission Yeast Fbh1. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004542
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004542

Souhrn

Zdroje

1. NewJH, SugiyamaT, ZaitsevaE, KowalczykowskiSC (1998) Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A. Nature 391: 407–410.

2. ShinoharaA, OgawaT (1998) Stimulation by Rad52 of yeast Rad51-mediated recombination. Nature 391: 404–407.

3. SungP (1997) Function of yeast Rad52 protein as a mediator between replication protein A and the Rad51 recombinase. J Biol Chem 272: 28194–28197.

4. WestSC, BensonFE, BaumannP (1998) Synergistic actions of Rad51 and Rad52 in recombination and DNA repair. Nature 391: 401–404.

5. 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.

6. San FilippoJ, ChiP, SehornMG, EtchinJ, KrejciL, et al. (2006) Recombination mediator and Rad51 targeting activities of a human BRCA2 polypeptide. J Biol Chem 281: 11649–11657.

7. AkamatsuY, DziadkowiecD, IkeguchiM, ShinagawaH, IwasakiH (2003) Two different Swi5-containing protein complexes are involved in mating-type switching and recombination repair in fission yeast. Proc Natl Acad Sci USA 100: 15770–15775.

8. AkamatsuY, TsutsuiY, MorishitaT, SiddiqueMSP, KurokawaY, et al. (2007) Fission yeast Swi5/Sfr1 and Rhp55/Rhp57 differentially regulate Rhp51-dependent recombination outcomes. EMBO J 26: 1352–1362.

9. AkamatsuY, JasinM (2010) Role for the mammalian Swi5-Sfr1 complex in DNA strand break repair through homologous recombination. PLoS Genet 6: e1001160.

10. HayaseA, TakagiM, MiyazakiT, OshiumiH, ShinoharaM, et al. (2004) A protein complex containing Mei5 and Sae3 promotes the assembly of the meiosis-specific RecA homolog Dmc1. Cell 119: 927–940.

11. TsubouchiH, RoederGS (2004) The budding yeast Mei5 and Sae3 proteins act together with Dmc1 during meiotic recombination. Genetics 168: 1219–1230.

12. HarutaN, KurokawaY, MurayamaY, AkamatsuY, UnzaiS, et al. (2006) The Swi5-Sfr1 complex stimulates Rhp51/Rad51- and Dmc1-mediated DNA strand exchange in vitro. Nat Struct Mol Biol 13: 823–830.

13. RongL, PalladinoF, AguileraA, KleinH (1991) The hyper-gene conversion hpr5-1 mutation of Saccharomyces cerevisiae is an allele of the SRS2/RADH gene. Genetics 127: 75–85.

14. SchiestlRH, PrakashS, PrakashL (1990) The SRS2 Suppressor of rad6 Mutations of Saccharomyces cerevisiae Acts by Channeling DNA Lesions Into the RAD52 DNA Repair Pathway. Genetics 124: 817–831.

15. AboussekhraA, ChanetR, ZgagaZ, Cassier-ChauvatC, HeudeM, et al. (1989) RADH, a gene of Saccharomyces cerevisiae encoding a putative DNA helicase involved in DNA repair. Characteristics of radH mutants and sequence of the gene. Nucleic Acids Res 17: 7211–7219.

16. MariniV, KrejciL (2010) Srs2: the “Odd-Job Man” in DNA repair. DNA Repair 9: 268–275.

17. KrejciL, van KomenS, LiY, VillemainJ, ReddyMS, et al. (2003) DNA helicase Srs2 disrupts the Rad51 presynaptic filament. Nature 423: 305–309.

18. VeauteX, JeussetJ, SoustelleC, KowalczykowskiSC, Le CamE, et al. (2003) The Srs2 helicase prevents recombination by disrupting Rad51 nucleoprotein filaments. Nature 423: 309–312.

19. DupaigneP, Le BretonC, FabreF, GangloffS, Le CamE, et al. (2008) The Srs2 helicase activity is stimulated by Rad51 filaments on dsDNA: implications for crossover incidence during mitotic recombination. Mol Cell 29: 243–254.

20. MoldovanG-L, DejsuphongD, PetalcorinMIR, HofmannK, TakedaS, et al. (2012) Inhibition of homologous recombination by the PCNA-interacting protein PARI. Mol Cell 45: 75–86.

21. WuL, HicksonID (2003) The Bloom's syndrome helicase suppresses crossing over during homologous recombination. Nature 426: 870–874.

22. IraG, MalkovaA, LiberiG, FoianiM, HaberJE (2003) Srs2 and Sgs1-Top3 suppress crossovers during double-strand break repair in yeast. Cell 115: 401–411.

23. BugreevDV, YuX, EgelmanEH, MazinAV (2007) Novel pro- and anti-recombination activities of the Bloom's syndrome helicase. Genes Dev 21: 3085–3094.

24. HuY, RaynardS, SehornMG, LuX, BussenW, et al. (2007) RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments. Genes Dev 21: 3073–3084.

25. ParkJS, ChoiE, LeeSH, LeeC, SeoYS (1997) A DNA helicase from Schizosaccharomyces pombe stimulated by single-stranded DNA-binding protein at low ATP concentration. J Biol Chem 272: 18910–18919.

26. MorishitaT, FurukawaF, SakaguchiC, TodaT, CarrAM, et al. (2005) Role of the Schizosaccharomyces pombe F-Box DNA helicase in processing recombination intermediates. Mol Cell Biol 25: 8074–8083.

27. OsmanF, DixonJ, BarrAR, WhitbyMC (2005) The F-Box DNA helicase Fbh1 prevents Rhp51-dependent recombination without mediator proteins. Mol Cell Biol 25: 8084–8096.

28. SakaguchiC, MorishitaT, ShinagawaH, HishidaT (2008) Essential and distinct roles of the F-box and helicase domains of Fbh1 in DNA damage repair. BMC Mol Biol 9: 27.

29. FuggerK, MistrikM, DanielsenJR, DinantC, FalckJ, et al. (2009) Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities. J Cell Biol 186: 655–663.

30. LaulierC, ChengA, HuangN, StarkJM (2010) Mammalian Fbh1 is important to restore normal mitotic progression following decatenation stress. DNA Repair 9: 708–717.

31. OkamotoS-Y, SatoM, TodaT, YamamotoM (2012) SCF Ensures Meiotic Chromosome Segregation Through a Resolution of Meiotic Recombination Intermediates. PLoS ONE 7: e30622.

32. KohzakiM, HatanakaA, SonodaE, YamazoeM, KikuchiK, et al. (2007) Cooperative roles of vertebrate Fbh1 and Blm DNA helicases in avoidance of crossovers during recombination initiated by replication fork collapse. Mol Cell Biol 27: 2812–2820.

33. LorenzA, OsmanF, FolkyteV, SofuevaS, WhitbyMC (2009) Fbh1 limits Rad51-dependent recombination at blocked replication forks. Mol Cell Biol 29: 4742–4756.

34. SunW, LorenzA, OsmanF, WhitbyMC (2011) A failure of meiotic chromosome segregation in a fbh1Δ mutant correlates with persistent Rad51-DNA associations. Nucleic Acids Res 39: 1718–1731.

35. KimJ, KimJ-H, LeeS-H, KimD-H, KangH-Y, et al. (2002) The novel human DNA helicase hFBH1 is an F-box protein. J Biol Chem 277: 24530–24537.

36. KimJ-H, KimJ, KimD-H, RyuG-H, BaeS-H, et al. (2004) SCFhFBH1 can act as helicase and E3 ubiquitin ligase. Nucleic Acids Res 32: 2287–2297.

37. LawrenceCL, JonesN, WilkinsonCRM (2009) Stress-induced phosphorylation of S. pombe Atf1 abrogates its interaction with F box protein Fbh1. Curr Biol 19: 1907–1911.

38. PruddenJ, EvansJS, HusseySP, DeansB, O'NeillP, et al. (2003) Pathway utilization in response to a site-specific DNA double-strand break in fission yeast. EMBO J 22: 1419–1430.

39. HopeJC, MenseSM, JalakasM, MitsumotoJ, FreyerGA (2006) Rqh1 blocks recombination between sister chromatids during double strand break repair, independent of its helicase activity. Proc Natl Acad Sci USA 103: 5875–5880.

40. FBH1 helicase disrupts RAD51 filaments in vitro and modulates homologous recombination in mammalian cells (2013) FBH1 helicase disrupts RAD51 filaments in vitro and modulates homologous recombination in mammalian cells. J Biol Chem 288: 34168–34180.

41. WangSW, GoodwinA, HicksonID, NorburyCJ (2001) Involvement of Schizosaccharomyces pombe Srs2 in cellular responses to DNA damage. Nucleic Acids Res 29: 2963–2972.

42. RobertT, DervinsD, FabreF, GangloffS (2006) Mrc1 and Srs2 are major actors in the regulation of spontaneous crossover. EMBO J 25: 2837–2846.

43. BacquinA, PouvelleC, SiaudN, PerderisetM, Salomé-DesnoulezS, et al. (2013) The helicase FBH1 is tightly regulated by PCNA via CRL4(Cdt2)-mediated proteolysis in human cells. Nucleic Acids Res 41: 6501–6513.

44. KurokawaY, MurayamaY, Haruta-TakahashiN, UrabeI, IwasakiH (2008) Reconstitution of DNA strand exchange mediated by Rhp51 recombinase and two mediators. PLoS Biol 6: e88.

45. Masuda-OzawaT, HoangT, SeoY-S, ChenL-F, SpiesM (2013) Single-molecule sorting reveals how ubiquitylation affects substrate recognition and activities of FBH1 helicase. Nucleic Acids Res 41: 3576–3587.

46. SkaarJR, PaganJK, PaganoM (2013) Mechanisms and function of substrate recruitment by F-box proteins. Nat Rev Mol Cell Biol 14: 369–381.

47. KusBM, CaldonCE, Andorn-BrozaR, EdwardsAM (2004) Functional interaction of 13 yeast SCF complexes with a set of yeast E2 enzymes in vitro. Proteins 54: 455–467.

48. ChioloI, SaponaroM, BaryshnikovaA, KimJ-H, SeoY-S, et al. (2007) The human F-Box DNA helicase FBH1 faces Saccharomyces cerevisiae Srs2 and postreplication repair pathway roles. Mol Cell Biol 27: 7439–7450.

49. SunW, NandiS, OsmanF, AhnJS, JakovleskaJ, et al. (2008) The FANCM ortholog Fml1 promotes recombination at stalled replication forks and limits crossing over during DNA double-strand break repair. Mol Cell 32: 118–128.

50. LorenzA, OsmanF, SunW, NandiS, SteinacherR, et al. (2012) The fission yeast FANCM ortholog directs non-crossover recombination during meiosis. Science 336: 1585–1588.

51. CrismaniW, GirardC, FrogerN, PradilloM, SantosJL, et al. (2012) FANCM limits meiotic crossovers. Science 336: 1588–1590.

52. PrakashR, SatoryD, DrayE, PapushaA, SchellerJ, et al. (2009) Yeast Mph1 helicase dissociates Rad51-made D-loops: implications for crossover control in mitotic recombination. Genes Dev 23: 67–79.

53. LiuJ, RenaultL, VeauteX, FabreF, StahlbergH, et al. (2011) Rad51 paralogues Rad55-Rad57 balance the antirecombinase Srs2 in Rad51 filament formation. Nature 479: 245–248.

54. KimWJ, LeeH, ParkEJ, ParkJK, ParkSD (2001) Gain- and loss-of-function of Rhp51, a Rad51 homolog in fission yeast, reveals dissimilarities in chromosome integrity. Nucleic Acids Res 29: 1724–1732.

55. MetzgerMB, WeissmanAM (2010) Working on a chain: E3s ganging up for ubiquitylation. Nat Cell Biol 12: 1124–1126.

56. YuanZM (1998) Regulation of Rad51 Function by c-Abl in Response to DNA Damage. Journal of Biological Chemistry 273: 3799–3802.

57. ChenG, YuanSS, LiuW, XuY, TrujilloK, et al. (1999) Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. J Biol Chem 274: 12748–12752.

58. SlupianekA, SchmutteC, TomblineG, Nieborowska-SkorskaM, HoserG, et al. (2001) BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance. Mol Cell 8: 795–806.

59. FlottS, KwonY, PigliYZ, RicePA, SungP, et al. (2011) Regulation of Rad51 function by phosphorylation. EMBO Rep 12: 833–839.

60. YataK, LloydJ, MaslenS, BleuyardJ-Y, SkehelM, et al. (2012) Plk1 and CK2 Act in Concert to Regulate Rad51 during DNA Double Strand Break Repair. Mol Cell 45: 371–383.

61. JeongY-T, RossiM, CermakL, SarafA, FlorensL, et al. (2013) FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress. J Cell Biol 200: 141–149.

62. MorenoS, KlarA, NurseP (1991) Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Meth Enzymol 194: 795–823.

63. CunninghamRP, DasGuptaC, ShibataT, RaddingCM (1980) Homologous pairing in genetic recombination: recA protein makes joint molecules of gapped circular DNA and closed circular DNA. Cell 20: 223–235.

64. HishidaT, HanY-W, ShibataT, KubotaY, IshinoY, et al. (2004) Role of the Escherichia coli RecQ DNA helicase in SOS signaling and genome stabilization at stalled replication forks. Genes Dev 18: 1886–1897.

65. FuruyaK, MiyabeI, TsutsuiY, PaderiF, KakushoN, et al. (2010) DDK phosphorylates checkpoint clamp component Rad9 and promotes its release from damaged chromatin. Mol Cell 40: 606–618.

66. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery (2006) A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. 439: 497–501.

67. LarkinMA, BlackshieldsG, BrownNP, ChennaR, McGettiganPA, et al. (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23: 2947–2948.

68. SaitouN, NeiM (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4: 406–425.