Rad51–Rad52 Mediated Maintenance of Centromeric Chromatin in

English version České info

The epigenetic mark of centromeres, CENP-A, is deposited in S phase in most yeasts by a mechanism that is not completely understood. Here, we identify two CEN7 flanking replication origins, ORI7-L1 and ORI7-RI, proximal to an early replicating centromere (CEN7) in a budding yeast Candida albicans. Replication forks starting from these origins stall randomly at CEN7 by the kinetochore that serves as a barrier to fork progression. We observe that centromeric fork stalling is reduced in absence of the HR proteins, Rad51 and Rad52, known to play a role in restarting stalled forks. Further, we demonstrate that Rad51 and Rad52 physically interact with CENP-ACaCse4 in vivo. CENP-ACaCse4 levels are reduced in absence of Rad51 or Rad52, which results in disruption of the kinetochore structure. Here we propose a novel DNA replication-coupled mechanism mediated by HR proteins which epigenetically maintains centromere identity by regulating CENP-A deposition. A direct role of DNA repair proteins in centromere function offers insights into the mechanisms of centromere mis-regulation that leads to widespread aneuploidy in cancer cells.

Vyšlo v časopise: Rad51–Rad52 Mediated Maintenance of Centromeric Chromatin in. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004344
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004344

Souhrn

Zdroje

1. EarnshawWC, MigeonBR (1985) Three related centromere proteins are absent from the inactive centromere of a stable isodicentric chromosome. Chromosoma 92 : 290–296.

2. AllshireRC, KarpenGH (2008) Epigenetic regulation of centromeric chromatin: old dogs, new tricks? Nat Rev Genet 9 : 923–937.

3. YamazakiS, HayanoM, MasaiH (2013) Replication timing regulation of eukaryotic replicons: Rif1 as a global regulator of replication timing. Trends Genet 29 : 449–460.

4. RaghuramanMK, WinzelerEA, CollingwoodD, HuntS, WodickaL, et al. (2001) Replication dynamics of the yeast genome. Science 294 : 115–121.

5. KorenA, TsaiHJ, TiroshI, BurrackLS, BarkaiN, et al. (2010) Epigenetically-inherited centromere and neocentromere DNA replicates earliest in S-phase. PLoS Genet 6: e1001068.

6. KimSM, DubeyDD, HubermanJA (2003) Early-replicating heterochromatin. Genes Dev 17 : 330–335.

7. TiengweC, MarcelloL, FarrH, DickensN, KellyS, et al. (2012) Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei. Cell Rep 2 : 185–197.

8. AravamudhanP, Felzer-KimI, JoglekarAP (2013) The Budding Yeast Point Centromere Associates with Two Cse4 Molecules during Mitosis. Curr Biol 23 : 770–774.

9. PearsonCG, YehE, GardnerM, OddeD, SalmonED, et al. (2004) Stable kinetochore-microtubule attachment constrains centromere positioning in metaphase. Curr Biol 14 : 1962–1967.

10. TakayamaY, SatoH, SaitohS, OgiyamaY, MasudaF, et al. (2008) Biphasic incorporation of centromeric histone CENP-A in fission yeast. Mol Biol Cell 19 : 682–690.

11. LandoD, EndesfelderU, BergerH, SubramanianL, DunnePD, et al. (2012) Quantitative single-molecule microscopy reveals that CENP-A(Cnp1) deposition occurs during G2 in fission yeast. Open Biol 2 : 120078.

12. GonzalezM, HeH, SunS, LiC, LiF (2013) Cell cycle-dependent deposition of CENP-A requires the Dos1/2-Cdc20 complex. Proc Natl Acad Sci U S A 110 : 606–611.

13. LivnyJ, YamaichiY, WaldorMK (2007) Distribution of centromere-like parS sites in bacteria: insights from comparative genomics. J Bacteriol 189 : 8693–8703.

14. VernisL, AbbasA, ChaslesM, GaillardinCM, BrunC, et al. (1997) An origin of replication and a centromere are both needed to establish a replicative plasmid in the yeast Yarrowia lipolytica. Mol Cell Biol 17 : 1995–2004.

15. SmithJG, CaddleMS, BulboacaGH, WohlgemuthJG, BaumM, et al. (1995) Replication of centromere II of Schizosaccharomyces pombe. Mol Cell Biol 15 : 5165–5172.

16. HayashiMT, TakahashiTS, NakagawaT, NakayamaJ, MasukataH (2009) The heterochromatin protein Swi6/HP1 activates replication origins at the pericentromeric region and silent mating-type locus. Nat Cell Biol 11 : 357–362.

17. GruberS, ErringtonJ (2009) Recruitment of condensin to replication origin regions by ParB/SpoOJ promotes chromosome segregation in B. subtilis. Cell 137 : 685–696.

18. KitamuraE, TanakaK, KitamuraY, TanakaTU (2007) Kinetochore microtubule interaction during S phase in Saccharomyces cerevisiae. Genes Dev 21 : 3319–3330.

19. PohlTJ, BrewerBJ, RaghuramanMK (2012) Functional centromeres determine the activation time of pericentric origins of DNA replication in Saccharomyces cerevisiae. PLoS Genet 8: e1002677.

20. NatsumeT, MullerCA, KatouY, RetkuteR, GierlinskiM, et al. (2013) Kinetochores coordinate pericentromeric cohesion and early DNA replication by cdc7-dbf4 kinase recruitment. Mol Cell 50 : 661–674.

21. GreenfederSA, NewlonCS (1992) Replication forks pause at yeast centromeres. Mol Cell Biol 12 : 4056–4066.

22. GreenfederSA, NewlonCS (1992) A replication map of a 61-kb circular derivative of Saccharomyces cerevisiae chromosome III. Mol Biol Cell 3 : 999–1013.

23. IvessaAS, LenzmeierBA, BesslerJB, GoudsouzianLK, SchnakenbergSL, et al. (2003) The Saccharomyces cerevisiae helicase Rrm3p facilitates replication past nonhistone protein-DNA complexes. Mol Cell 12 : 1525–1536.

24. KhakharRR, CobbJA, BjergbaekL, HicksonID, GasserSM (2003) RecQ helicases: multiple roles in genome maintenance. Trends Cell Biol 13 : 493–501.

25. LambertS, MizunoK, BlaisonneauJ, MartineauS, ChanetR, et al. (2010) Homologous recombination restarts blocked replication forks at the expense of genome rearrangements by template exchange. Mol Cell 39 : 346–359.

26. LambertS, WatsonA, SheedyDM, MartinB, CarrAM (2005) Gross chromosomal rearrangements and elevated recombination at an inducible site-specific replication fork barrier. Cell 121 : 689–702.

27. LabibK, HodgsonB (2007) Replication fork barriers: pausing for a break or stalling for time? EMBO Rep 8 : 346–353.

28. Gonzalez-PrietoR, Munoz-CabelloAM, Cabello-LobatoMJ, PradoF (2013) Rad51 replication fork recruitment is required for DNA damage tolerance. Embo J 32 : 1307–1321.

29. IrmischA, AmpatzidouE, MizunoK, O'ConnellMJ, MurrayJM (2009) Smc5/6 maintains stalled replication forks in a recombination-competent conformation. Embo J 28 : 144–155.

30. PerpelescuM, FukagawaT (2011) The ABCs of CENPs. Chromosoma 120 : 425–446.

31. BhattacharjeeS, OsmanF, FeeneyL, LorenzA, BryerC, et al. (2013) MHF1-2/CENP-S-X performs distinct roles in centromere metabolism and genetic recombination. Open Biol 3 : 130102.

32. NakamuraK, OkamotoA, KatouY, YadaniC, ShitandaT, et al. (2008) Rad51 suppresses gross chromosomal rearrangement at centromere in Schizosaccharomyces pombe. Embo J 27 : 3036–3046.

33. SanyalK, BaumM, CarbonJ (2004) Centromeric DNA sequences in the pathogenic yeast Candida albicans are all different and unique. Proc Natl Acad Sci U S A 101 : 11374–11379.

34. RoyB, SanyalK (2011) Diversity in requirement of genetic and epigenetic factors for centromere function in fungi. Eukaryot Cell 10 : 1384–1395.

35. BaumM, SanyalK, MishraPK, ThalerN, CarbonJ (2006) Formation of functional centromeric chromatin is specified epigenetically in Candida albicans. Proc Natl Acad Sci U S A 103 : 14877–14882.

36. PadmanabhanS, ThakurJ, SiddharthanR, SanyalK (2008) Rapid evolution of Cse4p-rich centromeric DNA sequences in closely related pathogenic yeasts, Candida albicans and Candida dubliniensis. Proc Natl Acad Sci U S A 105 : 19797–19802.

37. MishraPK, BaumM, CarbonJ (2007) Centromere size and position in Candida albicans are evolutionarily conserved independent of DNA sequence heterogeneity. Mol Genet Genomics 278 : 455–465.

38. ThakurJ, SanyalK (2013) Efficient neocentromere formation is suppressed by gene conversion to maintain centromere function at native physical chromosomal loci in Candida albicans. Genome Res 23 : 638–652.

39. KetelC, WangHS, McClellanM, BouchonvilleK, SelmeckiA, et al. (2009) Neocentromeres form efficiently at multiple possible loci in Candida albicans. PLoS Genet 5: e1000400.

40. HicksWM, KimM, HaberJE (2010) Increased mutagenesis and unique mutation signature associated with mitotic gene conversion. Science 329 : 82–85.

41. LopesM, Cotta-RamusinoC, PellicioliA, LiberiG, PlevaniP, et al. (2001) The DNA replication checkpoint response stabilizes stalled replication forks. Nature 412 : 557–561.

42. FachinettiD, BermejoR, CocitoA, MinardiS, KatouY, et al. (2010) Replication termination at eukaryotic chromosomes is mediated by Top2 and occurs at genomic loci containing pausing elements. Mol Cell 39 : 595–605.

43. WangY, VujcicM, KowalskiD (2001) DNA replication forks pause at silent origins near the HML locus in budding yeast. Mol Cell Biol 21 : 4938–4948.

44. ThakurJ, SanyalK (2012) A coordinated interdependent protein circuitry stabilizes the kinetochore ensemble to protect CENP-A in the human pathogenic yeast Candida albicans. PLoS Genet 8: e1002661.

45. AndaluzE, CiudadT, Gomez-RajaJ, CalderoneR, LarribaG (2006) Rad52 depletion in Candida albicans triggers both the DNA-damage checkpoint and filamentation accompanied by but independent of expression of hypha-specific genes. Mol Microbiol 59 : 1452–1472.

46. Garcia-PrietoF, Gomez-RajaJ, AndaluzE, CalderoneR, LarribaG (2011) Role of the homologous recombination genes RAD51 and RAD59 in the resistance of Candida albicans to UV light, radiomimetic and anti-tumor compounds and oxidizing agents. Fungal Genet Biol 47 : 433–445.

47. AndaluzE, BellidoA, Gomez-RajaJ, SelmeckiA, BouchonvilleK, et al. (2011) Rad52 function prevents chromosome loss and truncation in Candida albicans. Mol Microbiol 79 : 1462–1482.

48. JoglekarAP, BouckD, FinleyK, LiuX, WanY, et al. (2008) Molecular architecture of the kinetochore-microtubule attachment site is conserved between point and regional centromeres. J Cell Biol 181 : 587–594.

49. SanyalK, CarbonJ (2002) The CENP-A homolog CaCse4p in the pathogenic yeast Candida albicans is a centromere protein essential for chromosome transmission. Proc Natl Acad Sci U S A 99 : 12969–12974.

50. RoyB, BurrackLS, LoneMA, BermanJ, SanyalK (2011) CaMtw1, a member of the evolutionarily conserved Mis12 kinetochore protein family, is required for efficient inner kinetochore assembly in the pathogenic yeast Candida albicans. Mol Microbiol 80 : 14–32.

51. ZeitlinSG, BakerNM, ChapadosBR, SoutoglouE, WangJY, et al. (2009) Double-strand DNA breaks recruit the centromeric histone CENP-A. Proc Natl Acad Sci U S A 106 : 15762–15767.

52. ZeitlinSG, PatelS, KavliB, SlupphaugG (2005) Xenopus CENP-A assembly into chromatin requires base excision repair proteins. DNA Repair (Amst) 4 : 760–772.

53. FisherJK, BourniquelA, WitzG, WeinerB, PrentissM, et al. (2013) Four-dimensional imaging of E. coli nucleoid organization and dynamics in living cells. Cell 153 : 882–895.

54. ShangWH, HoriT, MartinsNM, ToyodaA, MisuS, et al. (2013) Chromosome engineering allows the efficient isolation of vertebrate neocentromeres. Dev Cell 24 : 635–648.

55. ScottKC (2014) Neocentromeres: a place for everything and everything in its place. Trends in Genetics 30 : 66–74.

56. CataniaS (2014) Anarchic centromeres: deciphering order from apparent chaos. Current Opinion in Cell Biology 26 : 41–50.

57. ThakurJ, SanyalK (2011) The essentiality of the fungus-specific Dam1 complex is correlated with a one-kinetochore-one-microtubule interaction present throughout the cell cycle, independent of the nature of a centromere. Eukaryot Cell 10 : 1295–1305.

58. OsmanF, WhitbyMC (2013) Emerging roles for centromere-associated proteins in DNA repair and genetic recombination. Biochem Soc Trans 41 : 1726–1730.

59. LiPC, PetreacaRC, JensenA, YuanJP, GreenMD, et al. (2013) Replication fork stability is essential for the maintenance of centromere integrity in the absence of heterochromatin. Cell Rep 3 : 638–645.

60. KatoT, SatoN, HayamaS, YamabukiT, ItoT, et al. (2007) Activation of Holliday junction recognizing protein involved in the chromosomal stability and immortality of cancer cells. Cancer Res 67 : 8544–8553.

61. Sanchez-PulidoL, PidouxAL, PontingCP, AllshireRC (2009) Common ancestry of the CENP-A chaperones Scm3 and HJURP. Cell 137 : 1173–1174.

62. MatsumotoS, OginoK, NoguchiE, RussellP, MasaiH (2005) Hsk1-Dfp1/Him1, the Cdc7-Dbf4 kinase in Schizosaccharomyces pombe, associates with Swi1, a component of the replication fork protection complex. J Biol Chem 280 : 42536–42542.

63. 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.

64. MarshallOJ, ChuehAC, WongLH, ChooKH (2008) Neocentromeres: new insights into centromere structure, disease development, and karyotype evolution. Am J Hum Genet 82 : 261–282.

65. WilsonRB, DavisD, MitchellAP (1999) Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J Bacteriol 181 : 1868–1874.

66. MuradAM, LeePR, BroadbentID, BarelleCJ, BrownAJ (2000) CIp10, an efficient and convenient integrating vector for Candida albicans. Yeast 16 : 325–327.

67. Gomez-RajaJ, DavisDA (2012) The beta-arrestin-like protein Rim8 is hyperphosphorylated and complexes with Rim21 and Rim101 to promote adaptation to neutral-alkaline pH. Eukaryot Cell 11 : 683–693.

68. DubeyDD, DavisLR, GreenfederSA, OngLY, ZhuJG, et al. (1991) Evidence suggesting that the ARS elements associated with silencers of the yeast mating-type locus HML do not function as chromosomal DNA replication origins. Mol Cell Biol 11 : 5346–5355.

69. KurtzMB, CortelyouMW, MillerSM, LaiM, KirschDR (1987) Development of autonomously replicating plasmids for Candida albicans. Mol Cell Biol 7 : 209–217.

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

71. TamuraK, NeiM, KumarS (2004) Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci U S A 101 : 11030–11035.

72. TamuraK, PetersonD, PetersonN, StecherG, NeiM, et al. (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28 : 2731–2739.

73. TakayamaY, MamnunYM, TrickeyM, DhutS, MasudaF, et al. (2010) Hsk1 -⁠ and SCF(Pof3)-dependent proteolysis of S. pombe Ams2 ensures histone homeostasis and centromere function. Dev Cell 18 : 385–396.