Rad59-Facilitated Acquisition of Y′ Elements by Short Telomeres Delays the Onset of Senescence

English version České info

In humans, telomerase is expressed in the germline and stem, but is repressed in somatic cells, which limits replicative lifespan of the latter. To unleash cell proliferation, telomerase is reactivated in most human cancers, but some cancer cells employ alternative lengthening of telomeres (ALT) based on homologous recombination (HR) to escape senescence. Recombination-based telomere maintenance similar to ALT was originally discovered in budding yeast deficient in telomerase activity. Two types of telomere arrangement that depend on two genetically distinct HR pathways (RAD51- and RAD59-dependent) were identified in post-senescent survivors, but the transition to telomere maintenance by HR is poorly understood. Here, we show that one of the earliest steps of short telomere rearrangement in telomerase-negative yeast is directly related to the “short telomere rescue pathway” proposed 20 years ago by Lundblad and Blackburn, which culminates in the acquisition of subtelomeric Y′ element by shortened telomere. We found that this telomere rearrangement depends on Rad52 strand annealing activity stimulated by Rad59, thus it is distinct from Rad51-dependent Y′ amplification process observed in type I survivors. We show that continuous repair of critically short telomeres in telomerase-negative cells delays the onset of senescence and prepares the ground for telomere maintenance by HR.

Vyšlo v časopise: Rad59-Facilitated Acquisition of Y′ Elements by Short Telomeres Delays the Onset of Senescence. PLoS Genet 10(11): e32767. doi:10.1371/journal.pgen.1004736
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004736

Souhrn

Zdroje

1. PalmW, de LangeT (2008) How Shelterin Protects Mammalian Telomeres. 42: 301–334 doi:10.1146/annurev.genet.41.110306.130350

2. PardoB, MarcandS (2005) Rap1 prevents telomere fusions by nonhomologous end joining. 24: 3117–3127 doi:10.1038/sj.emboj.7600778

3. BonettiD, MartinaM, ClericiM, LucchiniG, LongheseMP (2009) Multiple Pathways Regulate 3′ Overhang Generation at S. cerevisiae Telomeres. 35: 70–81 doi:10.1016/j.molcel.2009.05.015

4. XueY, RushtonMD, MaringeleL (2011) A novel checkpoint and RPA inhibitory pathway regulated by Rif1. 7: e1002417 doi:10.1371/journal.pgen.1002417

5. Ribeyre C, Shore D (2012) Anticheckpoint pathways at telomeres in yeast: 1–8. doi: 10.1038/nsmb.2225.

6. ChurikovD, CordaY, LucianoP, GéliV (2013) Cdc13 at a crossroads of telomerase action. 3: 39 doi:10.3389/fonc.2013.00039

7. IJpmaAS, GreiderCW (2003) Short telomeres induce a DNA damage response in Saccharomyces cerevisiae. 14: 987–1001 doi:10.1091/mbc.02-04-0057

8. AbdallahP, LucianoP, RungeKW, LisbyM, GéliV, et al. (2009) A two-step model for senescence triggered by a single critically short telomere. 11: 988–993 doi:10.1038/ncb1911

9. HectorRE, RayA, ChenB, ShtofmanR, BerknerKL, et al. (2012) Mec1p associates with functionally compromised telomeres. 121: 277–290 doi:10.1007/s00412-011-0359-0

10. LundbladV, BlackburnEH (1993) An alternative pathway for yeast telomere maintenance rescues est1- senescence. Cell 73: 347–60.

11. Teng S, Zakian V (1999) Telomere-telomere recombination is an efficient bypass pathway for telomere maintenance in Saccharomyces cerevisiae. Molecular and cellular biology.

12. TengSC, ZakianVA (1999) Telomere-telomere recombination is an efficient bypass pathway for telomere maintenance in Saccharomyces cerevisiae. 19: 8083–8093.

13. ChenQ, IjpmaA, GreiderCW (2001) Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events. 21: 1819–1827 doi:–10.1128/MCB.21.5.1819–1827.2001

14. TengSC, ChangJ, McCowanB, ZakianVA (2000) Telomerase-independent lengthening of yeast telomeres occurs by an abrupt Rad50p-dependent, Rif-inhibited recombinational process. 6: 947–952.

15. HuangP, PrydeFE, LesterD, MaddisonRL, BortsRH, et al. (2001) SGS1 is required for telomere elongation in the absence of telomerase. 11: 125–129.

16. JohnsonFB, MarciniakRA, McVeyM, StewartSA, HahnWC, et al. (2001) The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. 20: 905–913 doi:10.1093/emboj/20.4.905

17. McEachernMJ, HaberJE (2006) Break-induced replication and recombinational telomere elongation in yeast. 75: 111–135 doi:10.1146/annurev.biochem.74.082803.133234

18. LydeardJR, JainS, YamaguchiM, HaberJE (2007) Break-induced replication and telomerase-independent telomere maintenance require Pol32. 448: 820–823 doi:10.1038/nature06047

19. HuY, TangH, LiuN, TongX, DangW, et al. (2013) Telomerase-Null Survivor Screening Identifies Novel Telomere Recombination Regulators. PLoS Genet 9: e1003208 doi:10.1371/journal.pgen.1003208

20. McEachernMJ, IyerS (2001) Short telomeres in yeast are highly recombinogenic. 7: 695–704.

21. ChangM, DittmarJC, RothsteinR (2011) Long telomeres are preferentially extended during recombination-mediated telomere maintenance. 18: 451–456 doi:10.1038/nsmb.2034

22. FuX, DuanY, LiuY, CaiC, MengF, et al. (2014) Telomere recombination preferentially occurs at short telomeres in telomerase-null type II survivors. 9: e90644 doi:10.1371/journal.pone.0090644

23. DunnB, SzauterP, PardueML, SzostakJW (1984) Transfer of yeast telomeres to linear plasmids by recombination. 39: 191–201.

24. LouisEJ, HaberJE (1992) The structure and evolution of subtelomeric Y′ repeats in Saccharomyces cerevisiae. Genetics 131: 559–74.

25. Louis E, Naumova E, Lee A, Naumov G (1994) The chromosome end in yeast: its mosaic nature and influence on recombinational dynamics. Genetics.

26. KhadarooB, TeixeiraMT, LucianoP, Eckert-BouletN, GermannSM, et al. (2009) The DNA damage response at eroded telomeres and tethering to the nuclear pore complex. 11: 980–987 doi:10.1038/ncb1910

27. MorrishTA, GreiderCW (2009) Short telomeres initiate telomere recombination in primary and tumor cells. 5: e1000357 doi:10.1371/journal.pgen.1000357

28. Fallet E, Jolivet P, Soudet J, Lisby M, Gilson E, et al.. (2014) Length-dependent processing of telomeres in the absence of telomerase.: gkt1328. doi: 10.1093/nar/gkt1328.

29. LeS, MooreJK, HaberJE, GreiderCW (1999) RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase. 152: 143–152.

30. SandellLL, ZakianVA (1993) Loss of a yeast telomere: arrest, recovery, and chromosome loss. 75: 729–739.

31. BianchiA, ShoreD (2007) Early replication of short telomeres in budding yeast. 128: 1051–1062 doi:10.1016/j.cell.2007.01.041

32. MarcandS, BrevetV, GilsonE (1999) Progressive cis-inhibition of telomerase upon telomere elongation. 18: 3509–3519 doi:10.1093/emboj/18.12.3509

33. CohenH, SinclairDA (2001) Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase. 98: 3174–3179 doi:10.1073/pnas.061579598

34. ShampayJ, BlackburnEH (1988) Generation of telomere-length heterogeneity in Saccharomyces cerevisiae. 85: 534–538.

35. FörstemannK, HössM, LingnerJ (2000) Telomerase-dependent repeat divergence at the 3′ ends of yeast telomeres. 28: 2690–2694.

36. SugawaraN, IraG, HaberJE (2000) DNA length dependence of the single-strand annealing pathway and the role of Saccharomyces cerevisiae RAD59 in double-strand break repair. 20: 5300–5309.

37. LlorenteB, SmithCE, SymingtonLS (2008) Break-induced replication: what is it and what is it for? 7: 859–864.

38. WilsonMA, KwonY, XuY, ChungW, ChiP, et al. (2013) Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration. 502: 393–396 doi:10.1038/nature12585

39. WattPM, HicksonID, BortsRH, LouisEJ (1996) SGS1, a homologue of the Bloom's and Werner's syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae. Genetics 144: 935–45.

40. EnomotoS, GlowczewskiL, BermanJ (2002) MEC3, MEC1, and DDC2 are essential components of a telomere checkpoint pathway required for cell cycle arrest during senescence in Saccharomyces cerevisiae. Molecular biology of the cell 13: 2626–38 doi:10.1091/mbc.02-02-0012

41. TsaiY, TsengS, ChangS, LinC, TengS (2002) Involvement of replicative polymerases, Tel1p, Mec1p, Cdc13p, and the Ku complex in telomere-telomere recombination. Molecular and cellular biology 22: 5679–87.

42. WellingerRJ, ZakianVA (2012) Everything you ever wanted to know about Saccharomyces cerevisiae telomeres: beginning to end. 191: 1073–1105 doi:10.1534/genetics.111.137851

43. IraG, HaberJE (2002) Characterization of RAD51-independent break-induced replication that acts preferentially with short homologous sequences. 22: 6384–6392.

44. LouisEJ, HaberJE (1990) Mitotic recombination among subtelomeric Y′ repeats in Saccharomyces cerevisiae. Genetics 124: 547–59.

45. MottC, SymingtonLS (2011) RAD51-independent inverted-repeat recombination by a strand-annealing mechanism. 10: 408–415 doi:10.1016/j.dnarep.2011.01.007

46. MakovetsS, HerskowitzI, BlackburnEH (2004) Anatomy and dynamics of DNA replication fork movement in yeast telomeric regions. 24: 4019–4031.

47. ThamWH, WyitheJS, Ko FerrignoP, SilverPA, ZakianVA (2001) Localization of yeast telomeres to the nuclear periphery is separable from transcriptional repression and telomere stability functions. 8: 189–199.

48. FerreiraHC, LukeB, SchoberH, KalckV, LingnerJ, et al. (2011) The PIAS homologue Siz2 regulates perinuclear telomere position and telomerase activity in budding yeast. 13: 867–874 doi:10.1038/ncb2263

49. NagaiS, DavoodiN, GasserSM (2011) Nuclear organization in genome stability: SUMO connections. 21: 474–485 doi:10.1038/cr.2011.31

50. LundbladV (2002) Telomere maintenance without telomerase. 21: 522–531 doi:10.1038/sj.onc.1205079

51. SpellRM, Jinks-RobertsonS (2003) Role of mismatch repair in the fidelity of RAD51- and RAD59-dependent recombination in Saccharomyces cerevisiae. 165: 1733–1744.

52. RizkiA, LundbladV (2001) Defects in mismatch repair promote telomerase-independent proliferation. 411: 713–716 doi:10.1038/35079641

53. NatarajanS, McEachernMJ (2002) Recombinational telomere elongation promoted by DNA circles. 22: 4512–4521.

54. LiB, LustigAJ (1996) A novel mechanism for telomere size control in Saccharomyces cerevisiae. 10: 1310–1326.

55. PlattJM, RyvkinP, WanatJJ, DonahueG, RickettsMD, et al. (2013) Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence. 27: 1406–1420 doi:10.1101/gad.218776.113

56. SmithCD, SmithDL, DeRisiJL, BlackburnEH (2003) Telomeric protein distributions and remodeling through the cell cycle in Saccharomyces cerevisiae. 14: 556–570 doi:10.1091/mbc.E02-08-0457

57. SchoberH, KalckV, Vega-PalasMA, Van HouweG, SageD, et al. (2008) Controlled exchange of chromosomal arms reveals principles driving telomere interactions in yeast. 18: 261–271 doi:10.1101/gr.6687808

58. AgmonN, LiefshitzB, ZimmerC, FabreE, KupiecM (2013) Effect of nuclear architecture on the efficiency of double-strand break repair. 15: 694–699 doi:10.1038/ncb2745

59. BystrickyK, HeunP, GehlenL, LangowskiJ, GasserSM (2004) Long-range compaction and flexibility of interphase chromatin in budding yeast analyzed by high-resolution imaging techniques. 101: 16495–16500 doi:10.1073/pnas.0402766101

60. GilsonE, MüllerT, SogoJ, LarocheT, GasserSM (1994) RAP1 stimulates single- to double-strand association of yeast telomeric DNA: implications for telomere-telomere interactions. 22: 5310–5320.

61. LucianoP, CoulonS, FaureV, CordaY, BosJ, et al. (2012) RPA facilitates telomerase activity at chromosome ends in budding and fission yeasts. The EMBO journal 31: 2034–46 doi:10.1038/emboj.2012.40