Tel1 and Rif2 oppositely regulate telomere protection at uncapped telomeres in Saccharomyces cerevisiae

Ling-Li Zhang; Zhenfang Wu; Jin-Qiu Zhou

doi:10.1016/j.jgg.2018.09.001

Volume 45 Issue 9

Sep. 2018

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Tel1 and Rif2 oppositely regulate telomere protection at uncapped telomeres in Saccharomyces cerevisiae

doi: 10.1016/j.jgg.2018.09.001

a
CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
b
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China

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Corresponding author: E-mail address: zhenfang.wu@sibcb.ac.cn (Zhenfang Wu); E-mail address: jqzhou@sibcb.ac.cn (Jin-Qiu Zhou)
Received Date: 2018-06-02
Accepted Date: 2018-09-10
Rev Recd Date: 2018-09-06

Available Online: 2018-09-19

Publish Date: 2018-09-20

Abstract

Abstract

It has been well documented that Tel1 positively regulates telomere-end resection by promoting Mre11-Rad50-Xrs2 (MRX) activity, while Rif2 negatively regulates telomere-end resection by inhibiting MRX activity. At uncapped telomeres, whether Tel1 or Rif2 plays any role remains largely unknown. In this work, we examined the roles of Tel1 and Rif2 at uncapped telomeres in yku70Δ and/or cdc13-1 mutant cells cultured at non-permissive temperature. We found that deletion of TEL1 exacerbates the temperature sensitivity of both yku70Δ and cdc13-1 cells. Further epistasis analysis indicated that MRX and Tel1 function in the same pathway in telomere protection. Consistently, TEL1 deletion increases accumulation of Exo1-dependent telomeric single-stranded DNA (ssDNA) at uncapped telomeres, which stimulates checkpoint-dependent cell cycle arrest. Moreover, TEL1 deletion in yku70Δ cells facilitates Rad51-dependent Y′ recombination. In contrast, RIF2 deletion in yku70Δ cells decreases the accumulation of telomeric ssDNA after 8 h of incubation at the non-permissive temperature of 37 °C and suppresses the temperature sensitivity of yku70Δ cells, likely due to the increase of Mre11 association at telomeres. Collectively, our findings indicate that Tel1 and Rif2 regulate telomere protection at uncapped telomeres via their roles in balancing MRX activity in telomere resection.
- Tel1,
- Rif2,
- MRX,
- Uncapped telomeres,
- Telomere protection

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References(47)

References

[1]	Addinall, S.G., Holstein, E.M., Lawless, C. et al. Quantitative fitness analysis shows that NMD proteins and many other protein complexes suppress or enhance distinct telomere cap defects PLoS Genet., 7 (2011)
[2]	Anbalagan, S., Bonetti, D., Lucchini, G. et al. Rif1 supports the function of the CST complex in yeast telomere capping PLoS Genet., 7 (2011)
[3]	Bonetti, D., Clerici, M., Anbalagan, S. et al. PLoS Genet., 6 (2010)
[4]	Booth, C., Griffith, E., Brady, G. et al. Nucleic Acids Res., 29 (2001),pp. 4414-4422
[5]	Cervantes, R.B., Lundblad, V. Mechanisms of chromosome-end protection Curr. Opin. Cell Biol., 14 (2002),pp. 351-356
[6]	Chen, Q., Ijpma, A., Greider, C.W. Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events Mol. Cell. Biol., 21 (2001),pp. 1819-1827
[7]	de Lange, T. How telomeres solve the end-protection problem Science, 326 (2009),pp. 948-952
[8]	Duan, Y.M., Zhou, B.O., Peng, J. et al. J. Genet. Genomics, 43 (2016),pp. 451-465
[9]	Foster, S.S., Zubko, M.K., Guillard, S. et al. DNA Repair, 5 (2006),pp. 840-851
[10]	Gao, H., Toro, T.B., Paschini, M. et al. Genetics, 186 (2010),pp. 1147-1159
[11]	Garvik, B., Carson, M., Hartwell, L. Mol. Cell. Biol., 15 (1995),pp. 6128-6138
[12]	Grandin, N., Damon, C., Charbonneau, M. Ten1 functions in telomere end protection and length regulation in association with Stn1 and Cdc13 EMBO J., 20 (2001),pp. 1173-1183
[13]	Grandin, N., Reed, S.I., Charbonneau, M. Genes Dev., 11 (1997),pp. 512-527
[14]	Gravel, S., Larrivee, M., Labrecque, P. et al. Yeast Ku as a regulator of chromosomal DNA end structure Science, 280 (1998),pp. 741-744
[15]	Greider, C.W., Blackburn, E.H. Identification of a specific telomere terminal transferase activity in tetrahymena extracts Cell, 43 (1985),pp. 405-413
[16]	Hirano, Y., Fukunaga, K., Sugimoto, K. Rif1 and rif2 inhibit localization of tel1 to DNA ends Mol. Cell, 33 (2009),pp. 312-322
[17]	Hu, Y., Tang, H.B., Liu, N.N. et al. Telomerase-null survivor screening identifies novel telomere recombination regulators PLoS Genet., 9 (2013)
[18]	Kelleher, C., Teixeira, M.T., Forstemann, K. et al. Telomerase: biochemical considerations for enzyme and substrate Trends Biochem. Sci., 27 (2002),pp. 572-579
[19]	Larrivee, M., LeBel, C., Wellinger, R.J. The generation of proper constitutive G-tails on yeast telomeres is dependent on the MRX complex Genes Dev., 18 (2004),pp. 1391-1396
[20]	Levy, D.L., Blackburn, E.H. Mol. Cell. Biol., 24 (2004),pp. 10857-10867
[21]	Li, S., Makovets, S., Matsuguchi, T. et al. Cdk1-dependent phosphorylation of Cdc13 coordinates telomere elongation during cell-cycle progression Cell, 136 (2009),pp. 50-61
[22]	Lin, J.J., Zakian, V.A. Proc. Natl. Acad. Sci. U. S. A., 93 (1996),pp. 13760-13765
[23]	Lingner, J., Cooper, J.P., Cech, T.R. Telomerase and DNA end replication - no longer a lagging-strand problem Science, 269 (1995),pp. 1533-1534
[24]	Liu, C.C., Gopalakrishnan, V., Poon, L.F. et al. Cdk1 regulates the temporal recruitment of telomerase and Cdc13-Stn1-Ten1 complex for telomere replication Mol. Cell. Biol., 34 (2014),pp. 57-70
[25]	Liu, J., Huang, X.H., Withers, B.R. et al. Reducing sphingolipid synthesis orchestrates global changes to extend yeast lifespan Aging Cell, 12 (2013),pp. 833-841
[26]	Liu, Y.-Y., He, M.-H., Liu, J.-C. et al. J. Genet. Genomics, 45 (2018),pp. 247-257
[27]	Longtine, M.S., McKenzie, A., Demarini, D.J. et al. Yeast, 14 (1998),pp. 953-961
[28]	Mantiero, D., Clerici, M., Lucchini, G. et al. EMBO Rep., 8 (2007),pp. 380-387
[29]	Marcand, S., Brevet, V., Mann, C. et al. Cell cycle restriction of telomere elongation Curr. Biol., 10 (2000),pp. 487-490
[30]	Maringele, L., Lydall, D. Genes Dev., 16 (2002),pp. 1919-1933
[31]	Maringele, L., Lydall, D. Genetics, 166 (2004),pp. 1641-1649
[32]	Martina, M., Clerici, M., Baldo, V. et al. A balance between Tel1 and Rif2 activities regulates nucleolytic processing and elongation at telomeres Mol. Cell. Biol., 32 (2012),pp. 1604-1617
[33]	McEachern, M.J., Krauskopf, A., Blackburn, E.H. Telomeres and their control Annu. Rev. Genet., 34 (2000),pp. 331-358
[34]	Nakada, D., Matsumoto, K., Sugimoto, K. ATM-related Tel1 associates with double-strand breaks through an Xrs2-dependent mechanism Genes Dev., 17 (2003),pp. 1957-1962
[35]	Nugent, C.I., Bosco, G., Ross, L.O. et al. Telomere maintenance is dependent on activities required for end repair of double-strand breaks Curr. Biol., 8 (1998),pp. 657-662
[36]	Nugent, C.I., Hughes, T.R., Lue, N.F. et al. Cdc13p: a single-strand telomeric DNA-binding protein with a dual role in yeast telomere maintenance Science, 274 (1996),pp. 249-252
[37]	Ritchie, K.B., Petes, T.D. The Mre11p/Rad50p/Xrs2p complex and the Tel1p function in a single pathway for telomere maintenance in yeast Genetics, 155 (2000),pp. 475-479
[38]	Sabourin, M., Tuzon, C.T., Zakian, V.A. Mol. Cell, 27 (2007),pp. 550-561
[39]	Sikorski, R.S., Hieter, P. Genetics, 122 (1989),pp. 19-27
[40]	Teixeira, M.T., Arneric, M., Sperisen, P. et al. Telomere length homeostasis is achieved via a switch between telomerase-extendible and -nonextendible states Cell, 117 (2004),pp. 323-335
[41]	Teng, S.C., Zakian, V.A. Mol. Cell. Biol., 19 (1999),pp. 8083-8093
[42]	Tong, X.J., Li, Q.J., Duan, Y.M. et al. Est1 protects telomeres and inhibits subtelomeric Y'-element recombination Mol. Cell. Biol., 31 (2011),pp. 1263-1274
[43]	Vodenicharov, M.D., Wellinger, R.J. DNA degradation at unprotected telomeres in yeast is regulated by the CDK1 (Cdc28/CIb) cell-cycle kinase Mol. Cell, 24 (2006),pp. 127-137
[44]	Vodenicharov, M.D., Wellinger, R.J. The cell division cycle puts up with unprotected telomeres - cell cycle regulated telomere uncapping as a means to achieve telomere homeostasis Cell Cycle, 6 (2007),pp. 1161-1167
[45]	Watson, J.D. Origin of concatemeric T7 DNA Nat. New Biol., 239 (1972),pp. 197-201
[46]	Wotton, D., Shore, D. Genes Dev., 11 (1997),pp. 748-760
[47]	Wu, Z.F., Liu, J., Zhang, Q.D. et al. Rad6-Bre1-mediated H2B ubiquitination regulates telomere replication by promoting telomere-end resection Nucleic Acids Res., 45 (2017),pp. 3308-3322