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preLekára.sk / Odborné časopisy / PLOS Genetics / 2015 - 4

The Pif1 Helicase, a Negative Regulator of Telomerase, Acts Preferentially at Long Telomeres

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Telomerase, the enzyme that maintains telomeres, preferentially lengthens short telomeres. The baker’s yeast Pif1 DNA helicase inhibits both telomerase-mediated lengthening of existing telomeres and the formation of new telomeres at double strand breaks. By virtue of its ATPase activity, Pif1 reduces the level of telomerase binding to telomeres. Here, we report that the association of the telomerase subunits Est2 and Est1 at a DNA break was increased in the absence of Pif1, suggesting that Pif1 affects telomere length and new telomere formation by similar mechanisms. In cells lacking Pif1, Est2 and Est1 no longer bound preferentially to short telomeres, a larger fraction of telomeres was lengthened and the amount of telomeric DNA added per telomere was increased compared to wild type cells. Furthermore, by two different assays, Pif1 bound preferentially to long telomeres in vivo. Thus, preferential lengthening of short telomeres is achieved in part by targeting Pif1, a negative regulator of telomerase, to long telomeres.

Vyšlo v časopise: The Pif1 Helicase, a Negative Regulator of Telomerase, Acts Preferentially at Long Telomeres. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005186
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005186

Souhrn

Telomerase, the enzyme that maintains telomeres, preferentially lengthens short telomeres. The baker’s yeast Pif1 DNA helicase inhibits both telomerase-mediated lengthening of existing telomeres and the formation of new telomeres at double strand breaks. By virtue of its ATPase activity, Pif1 reduces the level of telomerase binding to telomeres. Here, we report that the association of the telomerase subunits Est2 and Est1 at a DNA break was increased in the absence of Pif1, suggesting that Pif1 affects telomere length and new telomere formation by similar mechanisms. In cells lacking Pif1, Est2 and Est1 no longer bound preferentially to short telomeres, a larger fraction of telomeres was lengthened and the amount of telomeric DNA added per telomere was increased compared to wild type cells. Furthermore, by two different assays, Pif1 bound preferentially to long telomeres in vivo. Thus, preferential lengthening of short telomeres is achieved in part by targeting Pif1, a negative regulator of telomerase, to long telomeres.

Zdroje

1. Lue NF. Plasticity of telomere maintenance mechanisms in yeast. Trends Biochem Sci. 2010;35:8–17. PubMed Central PMCID: PMC2818170. doi: 10.1016/j.tibs.2009.08.006 19846312

2. Marcand S, Brevet V, Mann C, Gilson E. Cell cycle restriction of telomere elongation. Curr Biol. 2000;10:487–90. 10801419

3. Diede SJ, Gottschling DE. Telomerase-mediated telomere addition in vivo requires DNA primase and DNA polymerases alpha and delta. Cell. 1999;99:723–33. 10619426

4. Taggart AKP, Teng S-C, Zakian VA. Est1p as a cell cycle-regulated activator of telomere-bound telomerase. Science. 2002;297:1023–6. 12169735

5. Tuzon CT, Wu Y, Chan A, Zakian VA. The Saccharomyces cerevisiae telomerase subunit Est3 binds telomeres in a cell cycle- and Est1-dependent manner and interacts directly with Est1 in vitro. PLoS Genet. 2011;7:e1002060. PubMed Central PMCID: PMCPMC3088721. doi: 10.1371/journal.pgen.1002060 21573139

6. Marcand S, Brevet V, Gilson E. Progressive cis-inhibition of telomerase upon telomere elongation. EMBO J. 1999;18:3509–19. 10369690

7. Teixeira MT, Arneric M, Sperisen P, Lingner J. Telomere length homeostasis is achieved via a switch between telomerase- extendible and-nonextendible states. Cell. 2004;117:323–35. 15109493

8. Sabourin M, Tuzon C, VA Z. Telomerase and Tel1p preferentially associate with short telomeres in S. cerevisiae. Mol Cell. 2007;27:550–61. PubMed Central PMCID: PMCPMC2650483. 17656141

9. Bianchi A, Shore D. Increased association of telomerase with short telomeres in yeast. Genes Dev. 2007;21:1726–30. PubMed 17639079.

10. Arneric M, Lingner J. Tel1 kinase and subtelomere-bound Tbf1 mediate preferential elongation of short telomeres by telomerase in yeast. EMBO Rep. 2007;8:1080–5. PubMed 17917674.

11. Hector R, Shtofman R, Ray A, Chen B, Nyun T, Berkner K, et al. Tel1p preferentially associates with short telomeres to stimulate their elongation. Mol Cell. 2007;27:851–8. 17803948

12. McGee J, Phillips J, Chan A, Sabourin M, Paeschke K, Zakian VA. Reduced Rif2 and lack of Mec1 target short telomeres for elongation rather than double-strand break repair. Nature Struct Molec Biol 2010;17:1438–45. PubMed Central PMCID: PMCPMC3058685. doi: 10.1038/nsmb.1947 21057524

13. Wotton D, Shore D. A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisiae. Genes Dev 1997;11:748–60. 9087429

14. Teng S-C, Chang J, McCowan B, Zakian VA. Telomerase-independent lengthening of yeast telomeres occurs by an abrupt Rad50p-dependent, Rif-inhibited recombinational process. Mol Cell. 2000;6:947–52. 11090632

15. Hirano Y, Fukunaga K, Sugimoto K. Rif1 and rif2 inhibit localization of tel1 to DNA ends. Mol Cell. 2009;33:312–22. Epub 2009/02/17. doi: S1097-2765(09)00024-0 [pii] doi: 10.1016/j.molcel.2008.12.027 PubMed 19217405.

16. Bochman ML, Sabouri N, Zakian VA. Unwinding the functions of the Pif1 family helicases. DNA Repair (Amst). 2010;9:237–49. PubMed Central PMCID: PMCPMC2853725. doi: 10.1016/j.dnarep.2010.01.008 20097624

17. Foury F, Lahaye A. Cloning and sequencing of the PIF gene involved in repair and recombination of yeast mitochondrial DNA. EMBO J. 1987;6:1441–9. 3038524

18. Zhou J-Q, Monson EM, Teng S- C, Schulz VP, Zakian VA. The Pif1p helicase, a catalytic inhibitor of telomerase lengthening of yeast telomeres. Science. 2000;289:771–4. PubMed Central PMCID: PMCPMID:10926538. 10926538

19. Schulz VP, Zakian VA. The Saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo telomere formation. Cell. 1994;76:145–55. PubMed Central PMCID: PMCPMID:8287473. 8287473

20. Myung K, Chen C, Kolodner RD. Multiple pathways cooperate in the suppression of genome instability in Saccharomyces cerevisiae. Nature. 2001;411:1073–6. PubMed Central PMCID: PMCPMID:11429610. 11429610

21. Makovets S, Blackburn EH. DNA damage signalling prevents deleterious telomere addition at DNA breaks. Nat Cell Biol. 2009;11:1383–6. Epub 2009/10/20. doi: ncb1985 [pii] doi: 10.1038/ncb1985 PubMed 19838171.

22. Boule J, Vega L, Zakian V. The Yeast Pif1p helicase removes telomerase from DNA. Nature. 2005;438:57–61. PubMed Central PMCID: PMCPMID:16121131. 16121131

23. Paeschke K, Bochman ML, Garcia PD, Cejka P, Friedman KL, Kowalczykowski SC, et al. Pif1 family helicases suppress genome instability at G-quadruplex motifs. Nature. 2013;497:458–62. PubMed Central PMCID: PMCPMC3680789. doi: 10.1038/nature12149 23657261

24. Saini N RS, Elango R, Ayyar S, Zhang Y, Deem A, Ira G, Haber JE, Lobachev KS, Malkova A. Migrating bubble during break-induced replication drives conservative DNA synthesis. Nature. 2013;502(7471):389–92. doi: 10.1038/nature12584 PubMed Central PMCID: PMCPMC3804423. 24025772

25. Wilson MA KY, Xu Y, Chung WH, Chi P, Niu H, Mayle R, Chen X, Malkova A, Sung P, Ira G. Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration. Nature. 2013;502(7471):393–6. doi: 10.1038/nature12585 PubMed Central PMCID: PMCPMC3915060. 24025768

26. Bianchi A, Negrini S, Shore D. Delivery of yeast telomerase to a DNA break depends on the recruitment functions of Cdc13 and Est1. Mol Cell. 2004;16:139–46. PubMed 15469829.

27. Forstemann K, Lingner J. Molecular basis for telomere repeat divergence in budding yeast. Mol Cell Biol. 2001;21:7277–86. PubMed 11585910.

28. Wang S-S, Zakian VA. Sequencing of Saccharomyces telomeres cloned using T4 DNA polymerase reveals two domains. Mol Cell Biol. 1990;10:4415–19. PubMed Central PMCID: PMCPMC361005. 2196453

29. Paeschke K, Capra JA, Zakian VA. DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase. Cell. 2011;145:678–91. PubMed Central PMCID: PMCPMC3129610. doi: 10.1016/j.cell.2011.04.015 21620135

30. Hemann MT, Strong MA, Hao LY, Greider CW. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell. 2001;107:67–77. 11595186

31. Prescott J, Blackburn E. Functionally interacting telomerase RNAs in the yeast telomerase complex. Genes Dev. 1997;11:2790–800. 9353249

32. Lingner J, Cech TR, Hughes TR, Lundblad V. Three Ever Shorter Telomere (EST) genes are dispensable for in vitro yeast telomerase activity. Proc Natl Acad Sci USA. 1997;94:11190–5. 9326584

33. Li JR YT, Chien IC, Lu CY, Lin JJ, Li HW. Pif1 regulates telomere length by preferentially removing telomerase from long telomere ends. Nucleic Acids Res. 2014;42(13):8527–36. doi: 10.1093/nar/gku541 PubMed Central PMCID: PMCPMC4117769. 24981509

34. Zahler AM, Williamson JR, Cech TR, Prescott DM. Inhibition of telomerase by G-quartet DNA structures. Nature. 1991;350:718–20. 2023635

35. Duan XL LN, Yang YT, Li HH, Li M, Dou SX, Xi XG. G-Quadruplexes Significantly Stimulate Pif1 Helicase-catalyzed Duplex DNA Unwinding. The Journal of Biological Chemistry. 2015. PubMed Central PMCID: PMCPMID: 25627683.

36. Ivessa AS, Lenzmeier BA, Bessler JB, Goudsouzian LK, Schnakenberg SL, Zakian VA. The Saccharomyces cerevisiae helicase Rrm3p facilitates replication past nonhistone protein-DNA complexes. Mol Cell. 2003;12:1525–36. PubMed Central PMCID: PMCPMID:14690605. 14690605

37. Sabouri N, McDonald KR, Webb CJ, Cristea IM, Zakian VA. DNA replication through hard-to-replicate sites, including both highly transcribed RNA Pol II and Pol III genes, requires the S. pombe Pfh1 helicase. Genes Dev. 2012;26:581–93. PubMed Central PMCID: PMCPMC3315119. doi: 10.1101/gad.184697.111 22426534

38. Boule JB, Zakian VA. The yeast Pif1p DNA helicase preferentially unwinds RNA DNA substrates. Nucleic Acids Res. 2007;35:5809–18. PubMed Central PMCID: PMCPMC2034482. 17720711

39. Zhou R ZJ, Bochman ML, Zakian VA, Ha T. Periodic DNA patrolling underlies diverse functions of Pif1 on R-loops and G-rich DNA. Elife. 2014;3. doi: 10.7554/eLife.02190 PubMed Central PMCID: PMCPMC3999857

40. Mozdy AD, Cech TR. Low abundance of telomerase in yeast: implications for telomerase haploinsufficiency. RNA. 2006;12:1721–37. PubMed 16894218.

41. Wu Y, Zakian VA. The telomeric Cdc13 protein interacts directly with the telomerase subunit Est1 to bring it to telomeric DNA ends in vitro. PNAS 2011;108:20362–9. PubMed Central PMCID: PMCPMC3251085. doi: 10.1073/pnas.1100281108 21969561

42. Tsukamoto Y, Taggart AKP, Zakian VA. The role of the Mre11-Rad50-Xrs2 complex in telomerase-mediated lengthening of Saccharomyces cerevisiae telomeres. Curr Biol. 2001;11:1328–35. 11553325

43. Sabourin M, Tuzon C, Fisher T, Zakian V. A flexible protein linker improves the function of epitope-tagged proteins in Saccharomyces cerevisiae. Yeast. 2007;24:39–45. 17192851

44. Gottschling DE, Aparicio OM, Billington BL, Zakian VA. Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell. 1990;63:751–62. PubMed Central PMCID: PMCPMID:2225075. 2225075

45. Goudsouzian L, Tuzon C, Zakian VA. S. cerevisiae Tel1p and Mre11p are required for normal levels of Est1p and Est2p telomere association. Mol Cell. 2006;24:603–10. 17188035

46. Fisher T, Taggart A, Zakian V. Cell cycle-dependent regulation of yeast telomerase by Ku. Nat Struct Mol Biol. 2004;11:1198–205. 15531893

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