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Biomolecules  2012 

Preserving Yeast Genetic Heritage through DNA Damage Checkpoint Regulation and Telomere Maintenance

DOI: 10.3390/biom2040505

Keywords: genome maintenance, DNA damage checkpoint, DNA damage response, double strand breaks (DSB), telomere

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Abstract:

In order to preserve genome integrity, extrinsic or intrinsic DNA damages must be repaired before they accumulate in cells and trigger other mutations and genome rearrangements. Eukaryotic cells are able to respond to different genotoxic stresses as well as to single DNA double strand breaks (DSBs), suggesting highly sensitive and robust mechanisms to detect lesions that trigger a signal transduction cascade which, in turn, controls the DNA damage response (DDR). Furthermore, cells must be able to distinguish natural chromosomal ends from DNA DSBs in order to prevent inappropriate checkpoint activation, DDR and chromosomal rearrangements. Since the original discovery of RAD9, the first DNA damage checkpoint gene identified in Saccharomyces cerevisiae, many genes that have a role in this pathway have been identified, including MRC1, MEC3, RAD24, RAD53, DUN1, MEC1 and TEL1. Extensive studies have established most of the genetic basis of the DNA damage checkpoint and uncovered its different functions in cell cycle regulation, DNA replication and repair, and telomere maintenance. However, major questions concerning the regulation and functions of the DNA damage checkpoint remain to be answered. First, how is the checkpoint activity coupled to DNA replication and repair? Second, how do cells distinguish natural chromosome ends from deleterious DNA DSBs? In this review we will examine primarily studies performed using Saccharomyces cerevisiae as a model system.

References

[1]  Ciccia, A.; Elledge, S.J. The DNA damage response: making it safe to play with knives. Mol. Cell 2010, 40, 179–204.
[2]  Zhou, B.B.; Elledge, S.J. The DNA damage response: putting checkpoints in perspective. Nature 2000, 408, 433–439, doi:10.1038/35044005.
[3]  Shiloh, Y. ATM and related protein kinases: safeguarding genome integrity. Nat. Rev. Cancer 2003, 3, 155–168, doi:10.1038/nrc1011.
[4]  Langerak, P.; Russell, P. Regulatory networks integrating cell cycle control with DNA damage checkpoints and double-strand break repair. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2011, 366, 3562–3571, doi:10.1098/rstb.2011.0070.
[5]  Flynn, R.L.; Zou, L. ATR: a master conductor of cellular responses to DNA replication stress. Trends Biochem. Sci. 2011, 36, 133–140, doi:10.1016/j.tibs.2010.09.005.
[6]  Lengauer, C.; Kinzler, K.W.; Vogelstein, B. Genetic instabilities in human cancers. Nature 1998, 396, 643–649, doi:10.1038/25292.
[7]  Kolodner, R.D.; Putnam, C.D.; Myung, K. Maintenance of genome stability in Saccharomyces cerevisiae. Science 2002, 297, 552–557, doi:10.1126/science.1075277.
[8]  Vessey, C.J.; Norbury, C.J.; Hickson, I.D. Genetic disorders associated with cancer predisposition and genomic instability. Prog. Nucleic Acid Res. Mol. Biol. 1999, 63, 189–221, doi:10.1016/S0079-6603(08)60723-0.
[9]  Bayani, J.; Squire, J.A. Advances in the detection of chromosomal aberrations using spectral karyotyping. Clin. Genet. 2001, 59, 65–73, doi:10.1034/j.1399-0004.2001.590201.x.
[10]  Deininger, P.L.; Batzer, M.A. Alu repeats and human disease. Mol. Genet. MeTable 1999, 67, 183–193, doi:10.1006/mgme.1999.2864.
[11]  Lindahl, T. Instability and decay of the primary structure of DNA. Nature 1993, 362, 709–715, doi:10.1038/362709a0.
[12]  Weinert, T.A.; Hartwell, L.H. The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science 1988, 241, 317–322.
[13]  Hartwell, L.H.; Weinert, T.A. Checkpoints: controls that ensure the order of cell cycle events. Science 1989, 246, 629–634.
[14]  Lowndes, N.F.; Murguia, J.R. Sensing and responding to DNA damage. Curr. Opin. Genet. Dev. 2000, 10, 17–25, doi:10.1016/S0959-437X(99)00050-7.
[15]  Bartek, J.; Lukas, J. DNA damage checkpoints: from initiation to recovery or adaptation. Curr. Opin. Cell Biol. 2007, 19, 238–245, doi:10.1016/j.ceb.2007.02.009.
[16]  Longhese, M.P.; Foiani, M.; Muzi-Falconi, M.; Lucchini, G.; Plevani, P. DNA damage checkpoint in budding yeast. EMBO J. 1998, 17, 5525–5528, doi:10.1093/emboj/17.19.5525.
[17]  Foiani, M.; Pellicioli, A.; Lopes, M.; Lucca, C.; Ferrari, M.; Liberi, G.; Muzi-Falconi, M.; Plevani1, P. DNA damage checkpoints and DNA replication controls in Saccharomyces cerevisiae. Mutat. Res. 2000, 451, 187–196, doi:10.1016/S0027-5107(00)00049-X.
[18]  Finn, K.; Lowndes, N.F.; Grenon, M. Eukaryotic DNA damage checkpoint activation in response to double-strand breaks. Cell Mol. Life Sci. 2012, 69, 1447–1473, doi:10.1007/s00018-011-0875-3.
[19]  Harper, J.W.; Elledge, S.J. The DNA damage response: ten years after. Mol. Cell 2007, 28, 739–745, doi:10.1016/j.molcel.2007.11.015.
[20]  Vinella, D.; D'Ari, R. Overview of controls in the Escherichia coli cell cycle. Bioessays. 1995, 17, 527–536, doi:10.1002/bies.950170609.
[21]  Lisby, M.; Barlow, J.H.; Burgess, R.C.; Rothstein, R. Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins. Cell 2004, 118, 699–713, doi:10.1016/j.cell.2004.08.015.
[22]  Mantiero, D.; Clerici, M.; Lucchini, G.; Longhese, M.P. Dual role for Saccharomyces cerevisiae Tel1 in the checkpoint response to double-strand breaks. EMBO Rep. 2007, 8, 380–387, doi:10.1038/sj.embor.7400911.
[23]  Lee, J.-H.; Paull, T.T. Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 2004, 304, 93–96, doi:10.1126/science.1091496.
[24]  Lee, J.-H.; Paull, T.T. ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 2005, 308, 551–554, doi:10.1126/science.1108297.
[25]  Fukunaga, K.; Kwon, Y.; Sung, P.; Sugimoto, K. Activation of protein kinase Tel1 through recognition of protein-bound DNA ends. Mol. Cell Biol. 2011, 31, 1959–1971, doi:10.1128/MCB.05157-11.
[26]  Shiotani, B.; Zou, L. Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol. Cell 2009, 33, 547–558, doi:10.1016/j.molcel.2009.01.024.
[27]  You, Z.; Chahwan, C.; Bailis, J.; Hunter, T.; Russell, P. ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol. Cell Biol. 2005, 25, 5363–5379, doi:10.1128/MCB.25.13.5363-5379.2005.
[28]  Zou, L.; Elledge, S.J. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 2003, 300, 1542–1548, doi:10.1126/science.1083430.
[29]  Jazayeri, A.; Falck, J.; Lukas, C.; Bartek, J.; Smith, G.C. M.; Lukas, J.; Jackson, S.P. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat. Cell Biol. 2006, 8, 37–45, doi:10.1038/ncb1337.
[30]  Kondo, T.; Matsumoto, K.; Sugimoto, K. Role of a complex containing Rad17, Mec3, and Ddc1 in the yeast DNA damage checkpoint pathway. Mol. Cell Biol. 1999, 19, 1136–1143.
[31]  Majka, J.; Burgers, P.M. J. The PCNA-RFC families of DNA clamps and clamp loaders. Prog. Nucleic Acid Res. Mol. Biol. 2004, 78, 227–260, doi:10.1016/S0079-6603(04)78006-X.
[32]  Lydall, D.; Weinert, T. G2/M checkpoint genes of Saccharomyces cerevisiae: Further evidence for roles in DNA replication and/or repair. Mol. Gen. Genet. 1997, 256, 638–651, doi:10.1007/s004380050612.
[33]  de, M.A.; Green, C.M.; Lowndes, N.F. RAD9 and RAD24 define two additive, interacting branches of the DNA damage checkpoint pathway in budding yeast normally required for Rad53 modification and activation. EMBO J. 1998, 17, 2687–2698, doi:10.1093/emboj/17.9.2687.
[34]  Green, C.M.; Erdjument-Bromage, H.; Tempst, P.; Lowndes, N.F. A novel Rad24 checkpoint protein complex closely related to replication factor C. Curr. Biol. 2000, 10, 39–42, doi:10.1016/S0960-9822(99)00263-8.
[35]  Crabbé, L.; Thomas, A.; Pantesco, V.; De Vos, J.; Pasero, P.; Lengronne, A. Analysis of replication profiles reveals key role of RFC-Ctf18 in yeast replication stress response. Nat. Struct. Mol. Biol. 2010, 17, 1391–1397, doi:10.1038/nsmb.1932.
[36]  Bellaoui, M.; Chang, M.; Ou, J.; Xu, H.; Boone, C.; Brown, G.W. Elg1 forms an alternative RFC complex important for DNA replication and genome integrity. EMBO J. 2003, 22, 4304–4313, doi:10.1093/emboj/cdg406.
[37]  Ben-Aroya, S.; Koren, A.; Liefshitz, B.; Steinlauf, R.; Kupiec, M. ELG1, a yeast gene required for genome stability, forms a complex related to replication factor C. Proc. Natl. Acad. Sci. USA 2003, 100, 9906–9911, doi:10.1073/pnas.1633757100.
[38]  Aroya, S.B.; Kupiec, M. The Elg1 replication factor C-like complex: A novel guardian of genome stability. DNA Repair (Amst.) 2005, 4, 409–417, doi:10.1016/j.dnarep.2004.08.003.
[39]  Kanellis, P.; Agyei, R.; Durocher, D. Elg1 forms an alternative PCNA-interacting RFC complex required to maintain genome stability. Curr. Biol. 2003, 13, 1583–1595, doi:10.1016/S0960-9822(03)00578-5.
[40]  Kumagai, A.; Lee, J.; Yoo, H.Y.; Dunphy, W.G. TopBP1 activates the ATR-ATRIP complex. Cell 2006, 124, 943–955, doi:10.1016/j.cell.2005.12.041.
[41]  Mordes, D.A.; Nam, E.A.; Cortez, D. Dpb11 activates the Mec1-Ddc2 complex. Proc. Natl. Acad. Sci. USA 2008, 105, 18730–18734.
[42]  Navadgi-Patil, V.M.; Burgers, P.M. Yeast DNA replication protein Dpb11 activates the Mec1/ATR checkpoint kinase. J. Biol. Chem. 2008, 283, 35853–35859.
[43]  Pfander, B.; Diffley, J.F. X. Dpb11 coordinates Mec1 kinase activation with cell cycle-regulated Rad9 recruitment. EMBO J. , 2011.
[44]  Wang, H.; Elledge, S.J. Genetic and physical interactions between DPB11 and DDC1 in the yeast DNA damage response pathway. Genetics 2002, 160, 1295–1304.
[45]  Puddu, F.; Granata, M.; Di Nola, L.; Balestrini, A.; Piergiovanni, G.; Lazzaro, F.; Giannattasio, M.; Plevani, P.; Muzi-Falconi, M. Phosphorylation of the budding yeast 9-1-1 complex is required for Dpb11 function in the full activation of the UV-induced DNA damage checkpoint. Mol. Cell Biol. 2008, 28, 4782–4793, doi:10.1128/MCB.00330-08.
[46]  Longhese, M.P.; Paciotti, V.; Fraschini, R.; Zaccarini, R.; Plevani, P.; Lucchini, G. The novel DNA damage checkpoint protein Ddc1p is phosphorylated periodically during the cell cycle and in response to DNA damage in budding yeast. EMBO J. 1997, 16, 5216–5226, doi:10.1093/emboj/16.17.5216.
[47]  Navadgi-Patil, V.M.; Burgers, P.M. The unstructured C-terminal tail of the 9-1-1 clamp subunit Ddc1 activates Mec1/ATR via two distinct mechanisms. Mol. Cell 2009, 36, 743–753.
[48]  Tanaka, K.; Russell, P. Mrc1 channels the DNA replication arrest signal to checkpoint kinase Cds1. Nat. Cell Biol. 2001, 3, 966–972.
[49]  Alcasabas, A.A.; Osborn, A.J.; Bachant, J.; Hu, F.; Werler, P.J.; Bousset, K.; Furuya, K.; Diffley, J.F.; Carr, A.M.; Elledge, S.J. Mrc1 transduces signals of DNA replication stress to activate Rad53. Nat. Cell Biol. 2001, 3, 958–965, doi:10.1038/ncb1101-958.
[50]  Schwartz, M.F.; Duong, J.K.; Sun, Z.; Morrow, J.S.; Pradhan, D.; Stern, D.F. Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint. Mol. Cell 2002, 9, 1055–1065, doi:10.1016/S1097-2765(02)00532-4.
[51]  Bando, M.; Katou, Y.; Komata, M.; Tanaka, H.; Itoh, T.; Sutani, T.; Shirahige, K. Csm3, Tof1, and Mrc1 form a heterotrimeric mediator complex that associates with DNA replication forks. J. Biol. Chem. 2009, 284, 34355–34365, doi:10.1074/jbc.M109.065730.
[52]  Tourrière, H.; Versini, G.; Cordón-Preciado, V.; Alabert, C.; Pasero, P. Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53. Mol. Cell 2005, 19, 699–706, doi:10.1016/j.molcel.2005.07.028.
[53]  Szyjka, S.J.; Viggiani, C.J.; Aparicio, O.M. Mrc1 is required for normal progression of replication forks throughout chromatin in S. cerevisiae. Mol. Cell 2005, 19, 691–697, doi:10.1016/j.molcel.2005.06.037.
[54]  Chen, S.-H.; Zhou, H. Reconstitution of Rad53 activation by Mec1 through adaptor protein Mrc1. J. Biol. Chem. 2009, 284, 18593–18604, doi:10.1074/jbc.M109.018242.
[55]  Berens, T.J.; Toczyski, D.P. Colocalization of Mec1 and Mrc1 is sufficient for Rad53 phosphorylation in vivo. Mol. Biol. Cell 2012, 23, 1058–1067, doi:10.1091/mbc.E11-10-0852.
[56]  Du, L.-L.; Nakamura, T.M.; Russell, P. Histone modification-dependent and -independent pathways for recruitment of checkpoint protein Crb2 to double-strand breaks. Genes Dev. 2006, 20, 1583–1596, doi:10.1101/gad.1422606.
[57]  Huyen, Y.; Zgheib, O.; Ditullio, R.A.; Gorgoulis, V.G.; Zacharatos, P.; Petty, T.J.; Sheston, E.A.; Mellert, H.S.; Stavridi, E.S.; Halazonetis, T.D. Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 2004, 432, 406–411, doi:10.1038/nature03114.
[58]  Manke, I.A.; Lowery, D.M.; Nguyen, A.; Yaffe, M.B. BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science 2003, 302, 636–639, doi:10.1126/science.1088877.
[59]  Yu, X.; Chini, C.C. S.; He, M.; Mer, G.; Chen, J. The BRCT domain is a phospho-protein binding domain. Science 2003, 302, 639–642, doi:10.1126/science.1088753.
[60]  Hammet, A.; Magill, C.; Heierhorst, J.; Jackson, S.P. Rad9 BRCT domain interaction with phosphorylated H2AX regulates the G1 checkpoint in budding yeast. EMBO Rep. 2007, 8, 851–857, doi:10.1038/sj.embor.7401036.
[61]  Bonilla, C.Y.; Melo, J.A.; Toczyski, D.P. Colocalization of sensors is sufficient to activate the DNA damage checkpoint in the absence of damage. Mol. Cell 2008, 30, 267–276, doi:10.1016/j.molcel.2008.03.023.
[62]  Wang, G.; Tong, X.; Weng, S.; Zhou, H. Multiple phosphorylation of Rad9 by CDK is required for DNA damage checkpoint activation. Cell Cycle 2012, 11, 3792–3800.
[63]  Lee, S.J.; Schwartz, M.F.; Duong, J.K.; Stern, D.F. Rad53 phosphorylation site clusters are important for Rad53 regulation and signaling. Mol. Cell Biol. 2003, 23, 6300–6314, doi:10.1128/MCB.23.17.6300-6314.2003.
[64]  Chen, S.-H.; Smolka, M.B.; Zhou, H. Mechanism of Dun1 activation by Rad53 phosphorylation in Saccharomyces cerevisiae. J. Biol. Chem. 2007, 282, 986–995.
[65]  Bashkirov, V.I.; Bashkirova, E.V.; Haghnazari, E.; Heyer, W.D. Direct kinase-to-kinase signaling mediated by the FHA phosphoprotein recognition domain of the Dun1 DNA damage checkpoint kinase. Mol. Cell Biol. 2003, 23, 1441–1452, doi:10.1128/MCB.23.4.1441-1452.2003.
[66]  Lee, H.; Yuan, C.; Hammet, A.; Mahajan, A.; Chen, E.S.-W.; Wu, M.-R.; Su, M.-I.; Heierhorst, J.; Tsai, M.-D. Diphosphothreonine-specific interaction between an SQ/TQ cluster and an FHA domain in the Rad53-Dun1 kinase cascade. Mol. Cell 2008, 30, 767–778, doi:10.1016/j.molcel.2008.05.013.
[67]  Lee, S.E.; Pellicioli, A.; Demeter, J.; Vaze, M.P.; Gasch, A.P.; Malkova, A.; Brown, P.O.; Botstein, D.; Stearns, T.; Foiani, M.; Haber, J.E. Arrest, adaptation, and recovery following a chromosome double-strand break in Saccharomyces cerevisia. Cold Spring Harb. Symp. Quant. Biol. 2000, 65, 303–314, doi:10.1101/sqb.2000.65.303.
[68]  Clémenson, C.; Marsolier-Kergoat, M.C. DNA damage checkpoint inactivation: adaptation and recovery. DNA Repair 2009, 8, 1101–1109, doi:10.1016/j.dnarep.2009.04.008.
[69]  Vaze, M.B.; Pellicioli, A.; Lee, S.E.; Ira, G.; Liberi, G.; Arbel-Eden, A.; Foiani, M.; Haber, J.E. Recovery from checkpoint-mediated arrest after repair of a double-strand break requires Srs2 helicase. Mol. Cell 2002, 10, 373–385, doi:10.1016/S1097-2765(02)00593-2.
[70]  Yeung, M.; Durocher, D. Srs2 enables checkpoint recovery by promoting disassembly of DNA damage foci from chromatin. DNA Repair 2011, 10, 1213–1222, doi:10.1016/j.dnarep.2011.09.005.
[71]  Keogh, M.-C.; Kim, J.-A.; Downey, M.; Fillingham, J.; Chowdhury, D.; Harrison, J.C.; Onishi, M.; Datta, N.; Galicia, S.; Emili, A.; Lieberman, J.; Shen, X.; Buratowski, S.; Haber, J.E.; Durocher, D.; Greenblatt, J.F.; Krogan, N.J. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature 2006, 439, 497–501.
[72]  O'Neill, B.M.; Szyjka, S.J.; Lis, E.T.; Bailey, A.O.; Yates, J.R.; Aparicio, O.M.; Romesberg, F.E. Pph3-Psy2 is a phosphatase complex required for Rad53 dephosphorylation and replication fork restart during recovery from DNA damage. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 9290–9295.
[73]  Woolstencroft, R.N.; Beilharz, T.H.; Cook, M.A.; Preiss, T.; Durocher, D.; Tyers, M. Ccr4 contributes to tolerance of replication stress through control of CRT1 mRNA poly(A) tail length. J. Cell Sci. 2006, 119, 5178–5192, doi:10.1242/jcs.03221.
[74]  Clerici, M.; Mantiero, D.; Lucchini, G.; Longhese, M.P. The Saccharomyces cerevisiae Sae2 protein promotes resection and bridging of double strand break ends. J. Biol. Chem. 2005, 280, 38631–38638.
[75]  Baroni, E.; Viscardi, V.; Cartagena-Lirola, H.; Lucchini, G.; Longhese, M.P. The functions of budding yeast Sae2 in the DNA damage response require Mec1- and Tel1-dependent phosphorylation. Mol. Cell Biol. 2004, 24, 4151–4165, doi:10.1128/MCB.24.10.4151-4165.2004.
[76]  Clerici, M.; Mantiero, D.; Lucchini, G.; Longhese, M.P. The Saccharomyces cerevisiae Sae2 protein negatively regulates DNA damage checkpoint signalling. EMBO Rep. 2006, 7, 212–218, doi:10.1038/sj.embor.7400593.
[77]  Leroy, C.; Lee, S.E.; Vaze, M.B.; Ochsenbein, F.; Ochsenbien, F.; Guérois, R.; Haber, J.E.; Marsolier-Kergoat, M.-C. PP2C phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a double-strand break. Mol. Cell 2003, 11, 827–835, doi:10.1016/S1097-2765(03)00058-3.
[78]  Smolka, M.B.; Chen, S.H.; Maddox, P.S.; Enserink, J.M.; Albuquerque, C.P.; Wei, X.X.; Desai, A.; Kolodner, R.D.; Zhou, H. An FHA domain-mediated protein interaction network of Rad53 reveals its role in polarized cell growth. J. Cell Biol. 2006, 175, 743–753, doi:10.1083/jcb.200605081.
[79]  Guillemain, G.; Ma, E.; Mauger, S.; Miron, S.; Thai, R.; Guérois, R.; Ochsenbein, F.; Marsolier-Kergoat, M.-C. Mechanisms of checkpoint kinase Rad53 inactivation after a double-strand break in Saccharomyces cerevisiae. Mol. Cell Biol. 2007, 27, 3378–3389, doi:10.1128/MCB.00863-06.
[80]  Bazzi, M.; Mantiero, D.; Trovesi, C.; Lucchini, G.; Longhese, M.P. Dephosphorylation of gamma H2A by Glc7/protein phosphatase 1 promotes recovery from inhibition of DNA replication. Mol. Cell Biol. 2010, 30, 131–145, doi:10.1128/MCB.01000-09.
[81]  Travesa, A.; Duch, A.; Quintana, D.G. Distinct phosphatases mediate the deactivation of the DNA damage checkpoint kinase Rad53. J. Biol. Chem. 2008, 283, 17123–17130, doi:10.1074/jbc.M801402200.
[82]  Kim, J.-A.; Hicks, W.M.; Li, J.; Tay, S.Y.; Haber, J.E. Protein phosphatases Pph3, Ptc2, and Ptc3 play redundant roles in DNA double-strand break repair by homologous recombination. Mol. Cell Biol. 2011, 31, 507–516, doi:10.1128/MCB.01168-10.
[83]  Toczyski, D.P.; Galgoczy, D.J.; Hartwell, L.H. CDC5 and CKII control adaptation to the yeast DNA damage checkpoint. Cell 1997, 90, 1097–1106, doi:10.1016/S0092-8674(00)80375-X.
[84]  Vidanes, G.M.; Sweeney, F.D.; Galicia, S.; Cheung, S.; Doyle, J.P.; Durocher, D.; Toczyski, D.P. CDC5 inhibits the hyperphosphorylation of the checkpoint kinase Rad53, leading to checkpoint adaptation. PLoS Biol. 2010, 8, e1000286, doi:10.1371/journal.pbio.1000286.
[85]  Tercero, J.A.; Longhese, M.P.; Diffley, J.F. X. A central role for DNA replication forks in checkpoint activation and response. Mol. Cell 2003, 11, 1323–1336, doi:10.1016/S1097-2765(03)00169-2.
[86]  Pellicioli, A.; Lee, S.E.; Lucca, C.; Foiani, M.; Haber, J.E. Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage-induced G2/M arrest. Mol. Cell 2001, 7, 293–300, doi:10.1016/S1097-2765(01)00177-0.
[87]  Myung, K.; Datta, A.; Kolodner, R.D. Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae. Cell 2001, 104, 397–408, doi:10.1016/S0092-8674(01)00227-6.
[88]  Craven, R.J.; Greenwell, P.W.; Dominska, M.; Petes, T.D. Regulation of genome stability by TEL1 and MEC1, yeast homologs of the mammalian ATM and ATR genes. Genetics 2002, 161, 493–507.
[89]  Mieczkowski, P.A.; Mieczkowska, J.O.; Dominska, M.; Petes, T.D. Genetic regulation of telomere-telomere fusions in the yeast Saccharomyces cerevisae. Proc. Natl. Acad. Sci. USA 2003, 100, 10854–10859, doi:10.1073/pnas.1934561100.
[90]  Smogorzewska, A.; de Lange, T. Regulation of telomerase by telomeric proteins. Annu. Rev. Biochem. 2004, 73, 177–208, doi:10.1146/annurev.biochem.73.071403.160049.
[91]  Vega, L.R.; Mateyak, M.K.; Zakian, V.A. Getting to the end: telomerase access in yeast and humans. Nat. Rev. Mol. Cell Biol. 2003, 4, 948–959.
[92]  Verdun, R.E.; Karlseder, J. Replication and protection of telomeres. Nature 2007, 447, 924–931, doi:10.1038/nature05976.
[93]  Nugent, C.I.; Hughes, T.R.; Lue, N.F.; Lundblad, V. Cdc13p: a single-strand telomeric DNA-binding protein with a dual role in yeast telomere maintenance. Science 1996, 274, 249–252, doi:10.1126/science.274.5285.249.
[94]  Lin, J.J.; Zakian, V.A. The Saccharomyces CDC13 protein is a single-strand TG1-3 telomeric DNA-binding protein in vitro that affects telomere behavior in vivo. Proc. Natl. Acad. Sci. USA 1996, 93, 13760–13765, doi:10.1073/pnas.93.24.13760.
[95]  Grandin, N.; Damon, C.; Charbonneau, M. Ten1 functions in telomere end protection and length regulation in association with Stn1 and Cdc13. EMBO J. 2001, 20, 1173–1183, doi:10.1093/emboj/20.5.1173.
[96]  Grandin, N.; Reed, S.I.; Charbonneau, M. Stn1, a new Saccharomyces cerevisiae protein, is implicated in telomere size regulation in association with Cdc13. Genes Dev. 1997, 11, 512–527, doi:10.1101/gad.11.4.512.
[97]  Sun, J.; Yu, E.Y.; Yang, Y.; Confer, L.A.; Sun, S.H.; Wan, K.; Lue, N.F.; Lei, M. Stn1-Ten1 is an Rpa2-Rpa3-like complex at telomeres. Genes Dev. 2009, 23, 2900–2914, doi:10.1101/gad.1851909.
[98]  Gao, H.; Cervantes, R.B.; Mandell, E.K.; Otero, J.H.; Lundblad, V. RPA-like proteins mediate yeast telomere function. Nat. Struct. Mol. Biol. 2007, 14, 208–214, doi:10.1038/nsmb1205.
[99]  Pennock, E.; Buckley, K.; Lundblad, V. Cdc13 delivers separate complexes to the telomere for end protection and replication. Cell 2001, 104, 387–396, doi:10.1016/S0092-8674(01)00226-4.
[100]  Taggart, A.K. P.; Teng, S.-C.; Zakian, V.A. Est1p as a cell cycle-regulated activator of telomere-bound telomerase. Science 2002, 297, 1023–1026, doi:10.1126/science.1074968.
[101]  Bonetti, D.; Martina, M.; Clerici, M.; Lucchini, G.; Longhese, M.P. Multiple pathways regulate 3' overhang generation at S. cerevisiae telomeres. Mol. Cell 2009, 35, 70–81, doi:10.1016/j.molcel.2009.05.015.
[102]  Zhu, Z.; Chung, W.-H.; Shim, E.Y.; Lee, S.E.; Ira, G. Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell 2008, 134, 981–994, doi:10.1016/j.cell.2008.08.037.
[103]  Mimitou, E.P.; Symington, L.S. Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing. Nature 2008, 455, 770–774, doi:10.1038/nature07312.
[104]  Ira, G.; Pellicioli, A.; Balijja, A.; Wang, X.; Fiorani, S.; Carotenuto, W.; Liberi, G.; Bressan, D.; Wan, L.; Hollingsworth, N.M.; Haber, J.E.; Foiani, M. DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1. Nature 2004, 431, 1011–1017, doi:10.1038/nature02964.
[105]  Chen, X.; Niu, H.; Chung, W.-H.; Zhu, Z.; Papusha, A.; Shim, E.Y.; Lee, S.E.; Sung, P.; Ira, G. Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation. Nat. Struct. Mol. Biol. 2011, 18, 1015–1019, doi:10.1038/nsmb.2105.
[106]  Huertas, P.; Cortés-Ledesma, F.; Sartori, A.A.; Aguilera, A.; Jackson, S.P. CDK targets Sae2 to control DNA-end resection and homologous recombination. Nature 2008, 455, 689–692, doi:10.1038/nature07215.
[107]  Bonetti, D.; Clerici, M.; Anbalagan, S.; Martina, M.; Lucchini, G.; Longhese, M.P. Shelterin-like proteins and Yku inhibit nucleolytic processing of Saccharomyces cerevisiae telomeres. PLoS Genet. 2010, 6, e1000966, doi:10.1371/journal.pgen.1000966.
[108]  Marcand, S.; Wotton, D.; Gilson, E.; Shore, D. Rap1p and telomere length regulation in yeast. Ciba Found. Symp. 1997, 211, 76–93. discussion 93-103.
[109]  Vodenicharov, M.D.; Laterreur, N.; Wellinger, R.J. Telomere capping in non-dividing yeast cells requires Yku and Rap1. EMBO J. 2010, 29, 3007–3019, doi:10.1038/emboj.2010.155.
[110]  Fisher, T.S.; Taggart, A.K. P.; Zakian, V.A. Cell cycle-dependent regulation of yeast telomerase by Ku. Nat. Struct. Mol. Biol. 2004, 11, 1198–1205, doi:10.1038/nsmb854.
[111]  Tuzon, C.T.; Wu, Y.; Chan, A.; Zakian, V.A. 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, doi:10.1371/journal.pgen.1002060.
[112]  Chan, A.; Boulé, J.-B.; Zakian, V.A. Two pathways recruit telomerase to Saccharomyces cerevisiae telomeres. PLoS Genet. 2008, 4, doi:10.1371/journal.pgen.1002060.
[113]  Qi, H.; Zakian, V.A. The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Genes Dev. 2000, 14, 1777–1788.
[114]  Li, S.; Makovets, S.; Matsuguchi, T.; Blethrow, J.D.; Shokat, K.M.; Blackburn, E.H. Cdk1-dependent phosphorylation of Cdc13 coordinates telomere elongation during cell-cycle progression. Cell 2009, 136, 50–61, doi:10.1016/j.cell.2008.11.027.
[115]  Gao, H.; Toro, T.B.; Paschini, M.; Braunstein-Ballew, B.; Cervantes, R.B.; Lundblad, V. Telomerase recruitment in Saccharomyces cerevisiae is not dependent on Tel1-mediated phosphorylation of Cdc13. Genetics 2010, 186, 1147–1159, doi:10.1534/genetics.110.122044.
[116]  Teixeira, M.T.; Arneric, M.; Sperisen, P.; Lingner, J. Telomere length homeostasis is achieved via a switch between telomerase- extendible and -nonextendible states. Cell 2004, 117, 323–335, doi:10.1016/S0092-8674(04)00334-4.
[117]  Levy, D.L.; Blackburn, E.H. Counting of Rif1p and Rif2p on Saccharomyces cerevisiae telomeres regulates telomere length. Mol. Cell Biol. 2004, 24, 10857–10867, doi:10.1128/MCB.24.24.10857-10867.2004.
[118]  McGee, J.S.; Phillips, J.A.; Chan, A.; Sabourin, M.; Paeschke, K.; Zakian, V.A. Reduced Rif2 and lack of Mec1 target short telomeres for elongation rather than double-strand break repair. Nat. Struct. Mol. Biol. 2010, 17, 1438–1445, doi:10.1038/nsmb.1947.
[119]  Wotton, D.; Shore, D. A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisia. Genes Dev. 1997, 11, 748–760, doi:10.1101/gad.11.6.748.
[120]  Sabourin, M.; Tuzon, C.T.; Zakian, V.A. Telomerase and Tel1p preferentially associate with short telomeres in S. cerevisiae. Mol. Cell 2007, 27, 550–561, doi:10.1016/j.molcel.2007.07.016.
[121]  Hector, R.E.; Shtofman, R.L.; Ray, A.; Chen, B.-R.; Nyun, T.; Berkner, K.L.; Runge, K.W. Tel1p preferentially associates with short telomeres to stimulate their elongation. Mol. Cell 2007, 27, 851–858, doi:10.1016/j.molcel.2007.08.007.
[122]  Bianchi, A.; Shore, D. Increased association of telomerase with short telomeres in yeast. Genes Dev. 2007, 21, 1726–1730, doi:10.1101/gad.438907.
[123]  Hirano, Y.; Fukunaga, K.; Sugimoto, K. Rif1 and Rif2 inhibit localization of tel1 to DNA ends. Mol. Cell 2009, 33, 312–322, doi:10.1016/j.molcel.2008.12.027.
[124]  Tseng, S.-F.; Lin, J.-J.; Teng, S.-C. The telomerase-recruitment domain of the telomere binding protein Cdc13 is regulated by Mec1p/Tel1p-dependent phosphorylation. Nucleic Acids Res. 2006, 34, 6327–6336.
[125]  Wu, Y.; Zakian, V.A. The telomeric Cdc13 protein interacts directly with the telomerase subunit Est1 to bring it to telomeric DNA ends in vitro. Proc. Natl. Acad. Sci. USA 2011, 108, 20362–20369, doi:10.1073/pnas.1100281108.
[126]  Smolka, M.B.; Albuquerque, C.P.; Chen, S.H.; Zhou, H. Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. Proc. Natl. Acad. Sci. USA. 2007, 104, 10364–10369, doi:10.1073/pnas.0701622104.
[127]  Longhese, M.P. DNA damage response at functional and dysfunctional telomeres. Genes Dev. 2008, 22, 125–140, doi:10.1101/gad.1626908.
[128]  Ribeyre, C.; Shore, D. Anticheckpoint pathways at telomeres in yeast. Nat. Struct. Mol. Biol. 2012, 19, 307–313.
[129]  Michelson, R.J.; Rosenstein, S.; Weinert, T. A telomeric repeat sequence adjacent to a DNA double-stranded break produces an anticheckpoint. Genes Dev. 2005, 19, 2546–2559, doi:10.1101/gad.1293805.
[130]  Xue, Y.; Rushton, M.D.; Maringele, L. A novel checkpoint and RPA inhibitory pathway regulated by Rif1. PLoS Genet. 2011, 7, doi:10.1371/journal.pgen.1002417.
[131]  Chen, S.H.; Albuquerque, C.P.; Liang, J.; Suhandynata, R.T.; Zhou, H. A proteome-wide analysis of kinase-substrate network in the DNA damage response. J. Biol. Chem. 2010, 285, 12803–12812.
[132]  Matsuoka, S.; Ballif, B.A.; Smogorzewska, A.; McDonald, E.R.; Hurov, K.E.; Luo, J.; Bakalarski, C.E.; Zhao, Z.; Solimini, N.; Lerenthal, Y.; Shiloh, Y.; Gygi, S.P.; Elledge, S.J. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 2007, 316, 1160–1166.

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