#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Roles of XRCC2, RAD51B and RAD51D in RAD51-Independent SSA Recombination


The repair of DNA double-strand breaks by recombination is key to the maintenance of genome integrity in all living organisms. Recombination can however generate mutations and chromosomal rearrangements, making the regulation and the choice of specific pathways of great importance. In addition to end-joining through non-homologous recombination pathways, DNA breaks are repaired by two homology-dependent pathways that can be distinguished by their dependence or not on strand invasion catalysed by the RAD51 recombinase. Working with the plant Arabidopsis thaliana, we present here an unexpected role in recombination for the Arabidopsis RAD51 paralogues XRCC2, RAD51B and RAD51D in the RAD51-independent single-strand annealing pathway. The roles of these proteins are seen in spontaneous and in DSB-induced recombination at a tandem direct repeat recombination tester locus, both of which are unaffected by the absence of RAD51. Individual roles of these proteins are suggested by the strikingly different severities of the phenotypes of the individual mutants, with the xrcc2 mutant being the most affected, and this is confirmed by epistasis analyses using multiple knockouts. Notwithstanding their clearly established importance for RAD51-dependent homologous recombination, XRCC2, RAD51B and RAD51D thus also participate in Single-Strand Annealing recombination.


Vyšlo v časopise: Roles of XRCC2, RAD51B and RAD51D in RAD51-Independent SSA Recombination. PLoS Genet 9(11): e32767. doi:10.1371/journal.pgen.1003971
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003971

Souhrn

The repair of DNA double-strand breaks by recombination is key to the maintenance of genome integrity in all living organisms. Recombination can however generate mutations and chromosomal rearrangements, making the regulation and the choice of specific pathways of great importance. In addition to end-joining through non-homologous recombination pathways, DNA breaks are repaired by two homology-dependent pathways that can be distinguished by their dependence or not on strand invasion catalysed by the RAD51 recombinase. Working with the plant Arabidopsis thaliana, we present here an unexpected role in recombination for the Arabidopsis RAD51 paralogues XRCC2, RAD51B and RAD51D in the RAD51-independent single-strand annealing pathway. The roles of these proteins are seen in spontaneous and in DSB-induced recombination at a tandem direct repeat recombination tester locus, both of which are unaffected by the absence of RAD51. Individual roles of these proteins are suggested by the strikingly different severities of the phenotypes of the individual mutants, with the xrcc2 mutant being the most affected, and this is confirmed by epistasis analyses using multiple knockouts. Notwithstanding their clearly established importance for RAD51-dependent homologous recombination, XRCC2, RAD51B and RAD51D thus also participate in Single-Strand Annealing recombination.


Zdroje

1. CoxMM, GoodmanMF, KreuzerKN, SherrattDJ, SandlerSJ, et al. (2000) The importance of repairing stalled replication forks. Nature 404: 37–41.

2. WhitakerSJ (1992) DNA damage by drugs and radiation: what is important and how is it measured? European journal of cancer 28: 273–276.

3. HeyerW-D, EhmsenKT, LiuJ (2010) Regulation of homologous recombination in eukaryotes. Annual review of genetics 44: 113–139.

4. WaterworthWM, DruryGE, BrayCM, WestCE (2011) Repairing breaks in the plant genome: the importance of keeping it together. The New phytologist 192: 805–822.

5. MassonJY, TarsounasMC, StasiakAZ, StasiakA, ShahR, et al. (2001) Identification and purification of two distinct complexes containing the five RAD51 paralogs. Genes & development 15: 3296–3307.

6. KrejciL, AltmannovaV, SpirekM, ZhaoX (2012) Homologous recombination and its regulation. Nucleic acids research 40: 5795–5818.

7. SuwakiN, KlareK, TarsounasM (2011) RAD51 paralogs: roles in DNA damage signalling, recombinational repair and tumorigenesis. Seminars in cell & developmental biology 22: 898–905.

8. ThackerJ (2005) The RAD51 gene family, genetic instability and cancer. Cancer letters 219: 125–135.

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

10. BernsteinKA, ReidRJD, SunjevaricI, DemuthK, BurgessRC, et al. (2011) The Shu complex, which contains Rad51 paralogues, promotes DNA repair through inhibition of the Srs2 anti-recombinase. Molecular biology of the cell 22: 1599–1607.

11. MartinV, ChahwanC, GaoH, BlaisV, WohlschlegelJ, et al. (2006) Sws1 is a conserved regulator of homologous recombination in eukaryotic cells. EMBO J 25: 2564–2574.

12. SasanumaH, TawaramotoMS, LaoJP, HosakaH, SandaE, et al. (2013) A new protein complex promoting the assembly of Rad51 filaments. Nature communications 4: 1676.

13. ShorE, WeinsteinJ, RothsteinR (2005) A genetic screen for top3 suppressors in Saccharomyces cerevisiae identifies SHU1, SHU2, PSY3 and CSM2: four genes involved in error-free DNA repair. Genetics 169: 1275–1289.

14. MankouriHW, NgoHP, HicksonID (2007) Shu proteins promote the formation of homologous recombination intermediates that are processed by Sgs1-Rmi1-Top3. Mol Biol Cell 18: 4062–4073.

15. GodinS, WierA, KabbinavarF, Bratton-PalmerDS, GhodkeH, et al. (2013) The Shu complex interacts with Rad51 through the Rad51 paralogues Rad55-Rad57 to mediate error-free recombination. Nucleic acids research 41: 4525–4534.

16. SheZ, GaoZQ, LiuY, WangWJ, LiuGF, et al. (2012) Structural and SAXS analysis of the budding yeast SHU-complex proteins. FEBS Lett 586: 2306–2312.

17. TaoY, LiX, LiuY, RuanJ, QiS, et al. (2012) Structural analysis of Shu proteins reveals a DNA binding role essential for resisting damage. J Biol Chem 287: 20231–20239.

18. LiuT, WanL, WuY, ChenJ, HuangJ (2011) hSWS1.SWSAP1 is an evolutionarily conserved complex required for efficient homologous recombination repair. J Biol Chem 286: 41758–41766.

19. BleuyardJ-Y, GallegoME, WhiteCI (2006) Recent advances in understanding of the DNA double-strand break repair machinery of plants. DNA repair 5: 1–12.

20. KarpenshifY, BernsteinKA (2012) From yeast to mammals: recent advances in genetic control of homologous recombination. DNA Repair (Amst) 11: 781–788.

21. GodthelpBC, WiegantWW, van Duijn-GoedhartA, SchärerOD, van BuulPPW, et al. (2002) Mammalian Rad51C contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability. Nucleic acids research 30: 2172–2182.

22. TakataM, SasakiMS, TachiiriS, FukushimaT, SonodaE, et al. (2001) Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs. Molecular and cellular biology 21: 2858–2866.

23. TakataM, SasakiMS, SonodaE, FukushimaT, MorrisonC, et al. (2000) The Rad51 paralog Rad51B promotes homologous recombinational repair. Molecular and cellular biology 20: 6476–6482.

24. JohnsonRD, LiuN, JasinM (1999) Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination. Nature 401: 397–399.

25. PierceAJ, JohnsonRD, ThompsonLH, JasinM (1999) XRCC3 promotes homology-directed repair of DNA damage in mammalian cells. Genes & development 13: 2633–2638.

26. LiuN, LamerdinJE, TebbsRS, SchildD, TuckerJD, et al. (1998) XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages. Molecular cell 1: 783–793.

27. TebbsRS, ZhaoY, TuckerJD, ScheererJB, SicilianoMJ, et al. (1995) Correction of chromosomal instability and sensitivity to diverse mutagens by a cloned cDNA of the XRCC3 DNA repair gene. Proceedings of the National Academy of Sciences of the United States of America 92: 6354–6358.

28. DeansB, GriffinCS, MaconochieM, ThackerJ (2000) Xrcc2 is required for genetic stability, embryonic neurogenesis and viability in mice. The EMBO journal 19: 6675–6685.

29. KuznetsovSG, HainesDC, MartinBK, SharanSK (2009) Loss of Rad51c leads to embryonic lethality and modulation of Trp53-dependent tumorigenesis in mice. Cancer Res 69: 863–872.

30. PittmanDL, SchimentiJC (2000) Midgestation lethality in mice deficient for the RecA-related gene, Rad51d/Rad51l3. Genesis 26: 167–173.

31. ShuZ, SmithS, WangL, RiceMC, KmiecEB (1999) Disruption of muREC2/RAD51L1 in mice results in early embryonic lethality which can Be partially rescued in a p53(-/-) background. Molecular and cellular biology 19: 8686–8693.

32. BleuyardJ-Y, WhiteCI (2004) The Arabidopsis homologue of Xrcc3 plays an essential role in meiosis. The EMBO journal 23: 439–449.

33. LiW, YangX, LinZ, TimofejevaL, XiaoR, et al. (2005) The AtRAD51C gene is required for normal meiotic chromosome synapsis and double-stranded break repair in Arabidopsis. Plant physiology 138: 965–976.

34. LiuN, SchildD, ThelenMP, ThompsonLH (2002) Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs in human cells. Nucleic acids research 30: 1009–1015.

35. MillerKA, SawickaD, BarskyD, AlbalaJS (2004) Domain mapping of the Rad51 paralog protein complexes. Nucleic acids research 32: 169–178.

36. MillerKA, YoshikawaDM, McConnellIR, ClarkR, SchildD, et al. (2002) RAD51C interacts with RAD51B and is central to a larger protein complex in vivo exclusive of RAD51. The Journal of biological chemistry 277: 8406–8411.

37. OsakabeK, AbeK, YamanouchiH, TakyuuT, YoshiokaT, et al. (2005) Arabidopsis Rad51B is important for double-strand DNA breaks repair in somatic cells. Plant molecular biology 57: 819–833.

38. OsakabeK, YoshiokaT, IchikawaH, TokiS (2002) Molecular cloning and characterization of RAD51-like genes from Arabidopsis thaliana. Plant molecular biology 50: 71–81.

39. SchildD, LioYC, CollinsDW, TsomondoT, ChenDJ (2000) Evidence for simultaneous protein interactions between human Rad51 paralogs. The Journal of biological chemistry 275: 16443–16449.

40. WieseC, CollinsDW, AlbalaJS, ThompsonLH, KronenbergA, et al. (2002) Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human cells. Nucleic acids research 30: 1001–1008.

41. BadieS, LiaoC, ThanasoulaM, BarberP, HillMA, et al. (2009) RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation. The Journal of cell biology 185: 587–600.

42. BrennemanMA, WagenerBM, MillerCA, AllenC, NickoloffJA (2002) XRCC3 controls the fidelity of homologous recombination: roles for XRCC3 in late stages of recombination. Molecular cell 10: 387–395.

43. ChunJ, BuechelmaierES, PowellSN (2013) Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway. Molecular and cellular biology 33: 387–395.

44. Da InesO, DegrooteF, AmiardS, GoubelyC, GallegoME, et al. (2013) Effects of XRCC2 and RAD51B mutations on somatic and meiotic recombination in Arabidopsis thaliana. The Plant Journal 74: 959–970.

45. LiuY, MassonJ-Y, ShahR, O'ReganP, WestSC (2004) RAD51C is required for Holliday junction processing in mammalian cells. Science 303: 243–246.

46. LiuY, TarsounasM, O'ReganP, WestSC (2007) Role of RAD51C and XRCC3 in genetic recombination and DNA repair. The Journal of biological chemistry 282: 1973–1979.

47. NagarajuG, HartlerodeA, KwokA, ChandramoulyG, ScullyR (2009) XRCC2 and XRCC3 regulate the balance between short- and long-tract gene conversions between sister chromatids. Molecular and cellular biology 29: 4283–4294.

48. RodrigueA, CoulombeY, JacquetK, GagneJP, RoquesC, et al. (2013) The RAD51 paralogs ensure cellular protection against mitotic defects and aneuploidy. J Cell Sci 126: 348–359.

49. ComptonSA, OzgurS, GriffithJD (2010) Ring-shaped Rad51 paralog protein complexes bind Holliday junctions and replication forks as visualized by electron microscopy. J Biol Chem 285: 13349–13356.

50. YokoyamaH, SaraiN, KagawaW, EnomotoR, ShibataT, et al. (2004) Preferential binding to branched DNA strands and strand-annealing activity of the human Rad51B, Rad51C, Rad51D and Xrcc2 protein complex. Nucleic acids research 32: 2556–2565.

51. IvanovEL, SugawaraN, Fishman-LobellJ, HaberJE (1996) Genetic requirements for the single-strand annealing pathway of double-strand break repair in Saccharomyces cerevisiae. Genetics 142: 693–704.

52. MansourWY, SchumacherS, RosskopfR, RheinT, Schmidt-PetersenF, et al. (2008) Hierarchy of nonhomologous end-joining, single-strand annealing and gene conversion at site-directed DNA double-strand breaks. Nucleic Acids Res 36: 4088–4098.

53. RothN, KlimeschJ, Dukowic-SchulzeS, PacherM, MannussA, et al. (2012) The requirement for recombination factors differs considerably between different pathways of homologous double-strand break repair in somatic plant cells. The Plant journal 72: 781–790.

54. StarkJM, PierceAJ, OhJ, PastinkA, JasinM (2004) Genetic steps of mammalian homologous repair with distinct mutagenic consequences. Mol Cell Biol 24: 9305–9316.

55. KroghBO, SymingtonLS (2004) Recombination proteins in yeast. Annual review of genetics 38: 233–271.

56. McDonaldJP, RothsteinR (1994) Unrepaired heteroduplex DNA in Saccharomyces cerevisiae is decreased in RAD1 RAD52-independent recombination. Genetics 137: 393–405.

57. MozlinAM, FungCW, SymingtonLS (2008) Role of the Saccharomyces cerevisiae Rad51 paralogs in sister chromatid recombination. Genetics 178: 113–126.

58. OrelN, KyrykA, PuchtaH (2003) Different pathways of homologous recombination are used for the repair of double-strand breaks within tandemly arranged sequences in the plant genome. The Plant Journal 35: 604–612.

59. CermakT, DoyleEL, ChristianM, WangL, ZhangY, et al. (2011) Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic acids research 39: e82.

60. HeacockM, SpanglerE, RihaK, PuizinaJ, ShippenDE (2004) Molecular analysis of telomere fusions in Arabidopsis: multiple pathways for chromosome end-joining. The EMBO journal 23: 2304–2313.

61. MillerJC, TanS, QiaoG, BarlowKA, WangJ, et al. (2011) A TALE nuclease architecture for efficient genome editing. Nature biotechnology 29: 143–148.

62. PuchtaH (2005) The repair of double-strand breaks in plants: mechanisms and consequences for genome evolution. Journal of experimental botany 56: 1–14.

63. SalomonS, PuchtaH (1998) Capture of genomic and T-DNA sequences during double-strand break repair in somatic plant cells. The EMBO journal 17: 6086–6095.

64. MalkovaA, IvanovEL, HaberJE (1996) Double-strand break repair in the absence of RAD51 in yeast: a possible role for break-induced DNA replication. Proc Natl Acad Sci U S A 93: 7131–7136.

65. WatanabeK, PacherM, DukowicS, SchubertV, PuchtaH, et al. (2009) The Structural Maintenance of Chromosomes 5/6 complex promotes sister chromatid alignment and homologous recombination after DNA damage in Arabidopsis thaliana. Plant Cell 21: 2688–2699.

66. Da InesO, DegrooteF, GoubelyC, AmiardS, GallegoME, et al. (2013) Meiotic Recombination in Arabidopsis Is Catalysed by DMC1, with RAD51 Playing a Supporting Role. PLoS genetics 9: e1003787.

67. YonetaniY, HocheggerH, SonodaE, ShinyaS, YoshikawaH, et al. (2005) Differential and collaborative actions of Rad51 paralog proteins in cellular response to DNA damage. Nucleic acids research 33: 4544–4552.

68. LioYC, MazinAV, KowalczykowskiSC, ChenDJ (2003) Complex formation by the human Rad51B and Rad51C DNA repair proteins and their activities in vitro. J Biol Chem 278: 2469–2478.

69. KurumizakaH, IkawaS, NakadaM, EnomotoR, KagawaW, et al. (2002) Homologous pairing and ring and filament structure formation activities of the human Xrcc2*Rad51D complex. J Biol Chem 277: 14315–14320.

70. SigurdssonS, Van KomenS, BussenW, SchildD, AlbalaJS, et al. (2001) Mediator function of the human Rad51B-Rad51C complex in Rad51/RPA-catalyzed DNA strand exchange. Genes Dev 15: 3308–3318.

71. TarsounasM, MunozP, ClaasA, SmiraldoPG, PittmanDL, et al. (2004) Telomere maintenance requires the RAD51D recombination/repair protein. Cell 117: 337–347.

72. LinFL, SperleK, SternbergN (1984) Model for homologous recombination during transfer of DNA into mouse L cells: role for DNA ends in the recombination process. Molec Cell Biol 4: 1020–1034.

73. PradoF, AguileraA (1995) Role of reciprocal exchange, one-ended invasion crossover and single-strand annealing on inverted and direct repeat recombination in yeast: different requirements for the RAD1, RAD10, and RAD52 genes. Genetics 139: 109–123.

74. BleuyardJ-Y, GallegoME, SavignyF, WhiteCI (2005) Differing requirements for the Arabidopsis Rad51 paralogs in meiosis and DNA repair. The Plant Journal 41: 533–545.

75. FauserF, RothN, PacherM, IlgG, Sánchez-FernándezR, et al. (2012) In planta gene targeting. Proceedings of the National Academy of Sciences of the United States of America 109: 7535–7540.

76. CurtisMD, GrossniklausU (2003) A gateway cloning vector set for high-throughput functional analysis of genes in planta. Plant physiology 133: 462–469.

77. CloughSJ, BentAF (1998) Floral dip: a simplified method for Agrobacterium-mediated transformation of Arabidopsis thaliana. The Plant Journal 16: 735–743.

78. GallegoME, WhiteCI (2001) RAD50 function is essential for telomere maintenance in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America 98: 1711–1716.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2013 Číslo 11
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#