CDC13

Summary

Gene Symbol: CDC13
Description: telomere-binding protein CDC13
Alias: EST4, telomere-binding protein CDC13
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Qi H, Zakian V. 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;14:1777-88 pubmed
    ..Point mutations in either CDC13 or POL1 that reduced the Cdc13p-Pol1p interaction resulted in telomerase mediated telomere lengthening...
  2. Zubko M, Lydall D. Linear chromosome maintenance in the absence of essential telomere-capping proteins. Nat Cell Biol. 2006;8:734-40 pubmed
    ..3' single-stranded overhang at telomeres include Pot1 in humans and fission yeast, TEBP in Oxytricha nova and Cdc13 in budding yeast...
  3. Polotnianka R, Li J, Lustig A. The yeast Ku heterodimer is essential for protection of the telomere against nucleolytic and recombinational activities. Curr Biol. 1998;8:831-4 pubmed
    ..Both Ku subunits genetically interacted with the putative single-stranded telomere-binding protein Cdc13p. We propose that Ku protects the telomere against nucleases and recombinases. ..
  4. Fisher T, Taggart A, Zakian V. Cell cycle-dependent regulation of yeast telomerase by Ku. Nat Struct Mol Biol. 2004;11:1198-205 pubmed
    ..These data support a model in which Ku recruits telomerase to telomeres in G1 phase when telomerase is inactive and promotes telomerase-mediated telomere lengthening in late S phase. ..
  5. Zhang W, Durocher D. De novo telomere formation is suppressed by the Mec1-dependent inhibition of Cdc13 accumulation at DNA breaks. Genes Dev. 2010;24:502-15 pubmed publisher
    ..Mec1 inhibits telomere healing by phosphorylating Cdc13 on its S306 residue, a phosphorylation event that suppresses Cdc13 accumulation at DSBs...
  6. Garvik B, Carson M, Hartwell L. Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Mol Cell Biol. 1995;15:6128-38 pubmed
    A cdc13 temperature-sensitive mutant of Saccharomyces cerevisiae arrests in the G2 phase of the cell cycle at the restrictive temperature as a result of DNA damage that activates the RAD9 checkpoint...
  7. Enomoto S, Glowczewski L, Lew Smith J, Berman J. Telomere cap components influence the rate of senescence in telomerase-deficient yeast cells. Mol Cell Biol. 2004;24:837-45 pubmed
    ..Increasing the levels of Stn1p and Ten1p in Upf+ cells is sufficient to delay senescence. In addition, cdc13-2 mutants exhibit delayed senescence rates similar to those of upfDelta cells...
  8. Zubko M, Guillard S, Lydall D. Exo1 and Rad24 differentially regulate generation of ssDNA at telomeres of Saccharomyces cerevisiae cdc13-1 mutants. Genetics. 2004;168:103-15 pubmed
    ..we examine the role of DNA repair and checkpoint genes in responding to unprotected telomeres in budding yeast cdc13-1 mutants...
  9. Grandin N, Damon C, Charbonneau M. Ten1 functions in telomere end protection and length regulation in association with Stn1 and Cdc13. EMBO J. 2001;20:1173-83 pubmed
    In Saccharomyces cerevisiae, Cdc13 has been proposed to mediate telomerase recruitment at telomere ends. Stn1, which associates with Cdc13 by the two-hybrid interaction, has been implicated in telomere maintenance...

More Information

Publications63

  1. Lin J, Zakian V. 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 U S A. 1996;93:13760-5 pubmed
    ..Cells lacking the activity of the essential gene CDC13 display a cell cycle arrest mediated by the DNA damage sensing, RAD9 cell cycle checkpoint, presumably because ..
  2. Vodenicharov M, Wellinger R. DNA degradation at unprotected telomeres in yeast is regulated by the CDK1 (Cdc28/Clb) cell-cycle kinase. Mol Cell. 2006;24:127-37 pubmed
    ..These results strongly suggest that after a loss of the telomere capping function, telomere-led genome instability is caused by tightly regulated cellular DNA repair attempts. ..
  3. Tsolou A, Lydall D. Mrc1 protects uncapped budding yeast telomeres from exonuclease EXO1. DNA Repair (Amst). 2007;6:1607-17 pubmed
    ..Our experiments show that Mrc1 contributes to the vitality of both cdc13-1 and yku70Delta telomere capping mutants...
  4. Deshpande A, Ivanova I, Raykov V, Xue Y, Maringele L. Polymerase epsilon is required to maintain replicative senescence. Mol Cell Biol. 2011;31:1637-45 pubmed publisher
    ..Every time resection and resynthesis switches, a fresh signal initiates, thus preventing checkpoint adaptation and ensuring the permanent character of senescence. ..
  5. Nugent C, Bosco G, Ross L, Evans S, Salinger A, Moore J, et al. Telomere maintenance is dependent on activities required for end repair of double-strand breaks. Curr Biol. 1998;8:657-60 pubmed
    ..Ku end-binding complex defined a third telomere-associated activity, required in parallel with telomerase [6] and Cdc13, a protein binding the single-strand portion of telomere DNA [7,8]...
  6. Mitchell M, Smith J, Mason M, Harper S, Speicher D, Johnson F, et al. Cdc13 N-terminal dimerization, DNA binding, and telomere length regulation. Mol Cell Biol. 2010;30:5325-34 pubmed publisher
    The essential yeast protein Cdc13 facilitates chromosome end replication by recruiting telomerase to telomeres, and together with its interacting partners Stn1 and Ten1, it protects chromosome ends from nucleolytic attack, thus ..
  7. Meier B, Driller L, Jaklin S, Feldmann H. New function of CDC13 in positive telomere length regulation. Mol Cell Biol. 2001;21:4233-45 pubmed
    Two roles for the Saccharomyces cerevisiae Cdc13 protein at the telomere have previously been characterized: it recruits telomerase to the telomere and protects chromosome ends from degradation...
  8. Tseng S, Lin J, Teng S. The telomerase-recruitment domain of the telomere binding protein Cdc13 is regulated by Mec1p/Tel1p-dependent phosphorylation. Nucleic Acids Res. 2006;34:6327-36 pubmed
    ..In addition, normal telomere length and growth could be restored by expressing a Cdc13-Est1p hybrid protein...
  9. Puglisi A, Bianchi A, Lemmens L, Damay P, Shore D. Distinct roles for yeast Stn1 in telomere capping and telomerase inhibition. EMBO J. 2008;27:2328-39 pubmed publisher
    The budding yeast Cdc13, Stn1 and Ten1 (CST) proteins are proposed to function as an RPA-like complex at telomeres that protects ('caps') chromosome ends and regulates their elongation by telomerase...
  10. Mason M, Wanat J, Harper S, Schultz D, Speicher D, Johnson F, et al. Cdc13 OB2 dimerization required for productive Stn1 binding and efficient telomere maintenance. Structure. 2013;21:109-120 pubmed publisher
    b>Cdc13 is an essential yeast protein required for telomere length regulation and genome stability. It does so via its telomere-capping properties and by regulating telomerase access to the telomeres...
  11. Grandin N, Charbonneau M. Mrc1, a non-essential DNA replication protein, is required for telomere end protection following loss of capping by Cdc13, Yku or telomerase. Mol Genet Genomics. 2007;277:685-99 pubmed
    Proteins involved in telomere end protection have previously been identified. In Saccharomyces cerevisiae, Cdc13, Yku and telomerase, mainly, prevent telomere uncapping, thus providing telomere stability and avoiding degradation and ..
  12. Wu Y, Zakian V. The telomeric Cdc13 protein interacts directly with the telomerase subunit Est1 to bring it to telomeric DNA ends in vitro. Proc Natl Acad Sci U S A. 2011;108:20362-9 pubmed publisher
    In Saccharomyces cerevisiae, a Cdc13-Est1 interaction is proposed to mediate recruitment of telomerase to DNA ends...
  13. Gardner R, Nelson Z, Gottschling D. Degradation-mediated protein quality control in the nucleus. Cell. 2005;120:803-15 pubmed
    ..We propose that San1p-mediated degradation acts as the last line of proteolytic defense against the deleterious accumulation of aberrant proteins in the nucleus and that analogous systems exist in other eukaryotes. ..
  14. Vodenicharov M, Laterreur N, Wellinger R. Telomere capping in non-dividing yeast cells requires Yku and Rap1. EMBO J. 2010;29:3007-19 pubmed publisher
    ..We show here that the essential Cdc13-Stn1-Ten1 complex is entirely dispensable for telomere protection in non-dividing cells...
  15. Li S, Makovets S, Matsuguchi T, Blethrow J, Shokat K, Blackburn E. Cdk1-dependent phosphorylation of Cdc13 coordinates telomere elongation during cell-cycle progression. Cell. 2009;136:50-61 pubmed publisher
    ..In budding yeast, Cdc13 plays an essential role in telomere length homeostasis, partly through its interactions with both the telomerase ..
  16. Takata H, Kanoh Y, Gunge N, Shirahige K, Matsuura A. Reciprocal association of the budding yeast ATM-related proteins Tel1 and Mec1 with telomeres in vivo. Mol Cell. 2004;14:515-22 pubmed
    ..Our study suggests a mechanistic similarity between telomere length regulation and DNA double-strand break repair, both of which are achieved by the direct association of PIKKs...
  17. Xue Y, Rushton M, Maringele L. A novel checkpoint and RPA inhibitory pathway regulated by Rif1. PLoS Genet. 2011;7:e1002417 pubmed publisher
    ..Our work has important implications for understanding the checkpoint and RPA-dependent DNA-damage responses in eukaryotic cells. ..
  18. Grandin N, Damon C, Charbonneau M. Cdc13 cooperates with the yeast Ku proteins and Stn1 to regulate telomerase recruitment. Mol Cell Biol. 2000;20:8397-408 pubmed
    The Saccharomyces cerevisiae CDC13 protein binds single-strand telomeric DNA. Here we report the isolation of new mutant alleles of CDC13 that confer either abnormal telomere lengthening or telomere shortening...
  19. Eldridge A, Wuttke D. Probing the mechanism of recognition of ssDNA by the Cdc13-DBD. Nucleic Acids Res. 2008;36:1624-33 pubmed publisher
    The Saccharomyces cerevisiae protein Cdc13 tightly and specifically binds the conserved G-rich single-stranded overhang at telomeres and plays an essential role in telomere end-protection and length regulation...
  20. Lendvay T, Morris D, Sah J, Balasubramanian B, Lundblad V. Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes. Genetics. 1996;144:1399-412 pubmed
    ..four complementation groups: the previously identified EST1 gene and three additional genes, called EST2, EST3 and EST4. Cloning of the EST2 gene demonstrated that it encodes a large, extremely basic novel protein with no motifs that ..
  21. Bonetti D, Clerici M, Anbalagan S, Martina M, Lucchini G, Longhese M. Shelterin-like proteins and Yku inhibit nucleolytic processing of Saccharomyces cerevisiae telomeres. PLoS Genet. 2010;6:e1000966 pubmed publisher
    ..Thus, chromosome end degradation is controlled by telomeric proteins that specifically inhibit the action of different nucleases. ..
  22. Zhang T, Nirantar S, Lim H, Sinha I, Surana U. DNA damage checkpoint maintains CDH1 in an active state to inhibit anaphase progression. Dev Cell. 2009;17:541-51 pubmed publisher
    ..Hence, the DNA damage checkpoint suppresses both cohesin cleavage and spindle elongation to preserve chromosome stability. ..
  23. Gravel S, Larrivee M, Labrecque P, Wellinger R. Yeast Ku as a regulator of chromosomal DNA end structure. Science. 1998;280:741-4 pubmed
    ..Because Ku-mediated DNA end joining involving telomeres would result in chromosome instability, our data also suggest that Ku has a distinct function when bound to telomeres. ..
  24. Maringele L, Lydall D. EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Delta mutants. Genes Dev. 2002;16:1919-33 pubmed
    ..This link is confirmed by our demonstration that EXO1 also plays a role in ssDNA generation in cdc13-1 mutants...
  25. Hsu C, Chen Y, Tsai S, Tu P, Wang M, Lin J. Interaction of Saccharomyces Cdc13p with Pol1p, Imp4p, Sir4p and Zds2p is involved in telomere replication, telomere maintenance and cell growth control. Nucleic Acids Res. 2004;32:511-21 pubmed
    ..The function of the N-terminal 1-252 region of Cdc13p was also analyzed. Expressing Cdc13(252-924)p, which lacks amino acids 1-252 of Cdc13p, causes defects in progressive cell growth and eventually ..
  26. Grandin N, Reed S, Charbonneau M. Stn1, a new Saccharomyces cerevisiae protein, is implicated in telomere size regulation in association with Cdc13. Genes Dev. 1997;11:512-27 pubmed
    We have isolated STN1, an essential Saccharomyces cerevisiae gene, as a suppressor of the cdc13-1 mutation. A synthetic lethal interaction between a temperature-sensitive mutant allele of STN1, stn1-13, and cdc13-1 was observed...
  27. Grandin N, Damon C, Charbonneau M. Cdc13 prevents telomere uncapping and Rad50-dependent homologous recombination. EMBO J. 2001;20:6127-39 pubmed
    b>Cdc13 performs an essential function in telomere end protection in budding yeast. Here, we analyze the consequences on telomere dynamics of cdc13-induced telomeric DNA damage in proliferating cells...
  28. Ngo H, Lydall D. Survival and growth of yeast without telomere capping by Cdc13 in the absence of Sgs1, Exo1, and Rad9. PLoS Genet. 2010;6:e1001072 pubmed publisher
    ..Telomere capping proteins, such as Cdc13 and POT1, are essential for the viability of budding yeast and mammalian cells, respectively...
  29. Qi H, Li T, Kuo D, Nur E Kamal A, Liu L. Inactivation of Cdc13p triggers MEC1-dependent apoptotic signals in yeast. J Biol Chem. 2003;278:15136-41 pubmed
    Inactivation of the budding yeast telomere binding protein Cdc13 results in abnormal telomeres (exposed long G-strands) and activation of the DNA damage checkpoint...
  30. Downey M, Houlsworth R, Maringele L, Rollie A, Brehme M, Galicia S, et al. A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator. Cell. 2006;124:1155-68 pubmed
    ..involved in telomere capping, we carried out a genome-wide screen in Saccharomyces cerevisiae for suppressors of cdc13-1, an allele of the telomere-capping protein Cdc13...
  31. Hirano Y, Sugimoto K. Cdc13 telomere capping decreases Mec1 association but does not affect Tel1 association with DNA ends. Mol Biol Cell. 2007;18:2026-36 pubmed
    ..In budding yeast, Mec1 and Tel1 correspond to ATR and ATM, respectively. Here, we show that Cdc13-dependent telomere capping attenuates Mec1 association with DNA ends...
  32. Bourns B, Alexander M, Smith A, Zakian V. Sir proteins, Rif proteins, and Cdc13p bind Saccharomyces telomeres in vivo. Mol Cell Biol. 1998;18:5600-8 pubmed
    ..The data support models in which the telomere acts as an initiation site for TPE by recruiting silencing proteins to the chromosome end. ..
  33. Tsukamoto Y, Taggart A, Zakian V. The role of the Mre11-Rad50-Xrs2 complex in telomerase- mediated lengthening of Saccharomyces cerevisiae telomeres. Curr Biol. 2001;11:1328-35 pubmed
    ..Rather, the data suggest that the MRX complex is involved in recruiting telomerase activity to yeast telomeres. ..
  34. Anbalagan S, Bonetti D, Lucchini G, Longhese M. Rif1 supports the function of the CST complex in yeast telomere capping. PLoS Genet. 2011;7:e1002024 pubmed publisher
    Telomere integrity in budding yeast depends on the CST (Cdc13-Stn1-Ten1) and shelterin-like (Rap1-Rif1-Rif2) complexes, which are thought to act independently from each other...
  35. Sun J, Yang Y, Wan K, Mao N, Yu T, Lin Y, et al. Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase ?. Cell Res. 2011;21:258-74 pubmed publisher
    Budding yeast Cdc13-Stn1-Ten1 (CST) complex plays an essential role in telomere protection and maintenance, and has been proposed to be a telomere-specific replication protein A (RPA)-like complex...
  36. Pennock E, Buckley K, Lundblad V. Cdc13 delivers separate complexes to the telomere for end protection and replication. Cell. 2001;104:387-96 pubmed
    In Saccharomyces cerevisiae, the telomere binding protein Cdc13 mediates telomere replication by recruiting telomerase, and also performs an essential function in chromosome end protection...
  37. Zappulla D, Roberts J, Goodrich K, Cech T, Wuttke D. Inhibition of yeast telomerase action by the telomeric ssDNA-binding protein, Cdc13p. Nucleic Acids Res. 2009;37:354-67 pubmed publisher
  38. Dewar J, Lydall D. Pif1- and Exo1-dependent nucleases coordinate checkpoint activation following telomere uncapping. EMBO J. 2010;29:4020-34 pubmed publisher
    ..Using the cdc13-1 mutation to conditionally 'uncap' telomeres in budding yeast, we show that the telomere capping protein Cdc13 ..
  39. Petreaca R, Chiu H, Eckelhoefer H, Chuang C, Xu L, Nugent C. Chromosome end protection plasticity revealed by Stn1p and Ten1p bypass of Cdc13p. Nat Cell Biol. 2006;8:748-55 pubmed
    ..Two Cdc13-interacting proteins, Stn1p and Ten1p, are also required for viability and telomere length regulation...
  40. Petreaca R, Chiu H, Nugent C. The role of Stn1p in Saccharomyces cerevisiae telomere capping can be separated from its interaction with Cdc13p. Genetics. 2007;177:1459-74 pubmed
    ..Thus, an amino-terminal region of Stn1p is sufficient for its essential function, while a central region of Stn1p either negatively regulates the STN1 essential function or destabilizes the mutant Stn1 protein. ..
  41. Wood M, Sanchez Y. Deregulated Ras signaling compromises DNA damage checkpoint recovery in S. cerevisiae. Cell Cycle. 2010;9:3353-63 pubmed publisher
    ..This work identifies a new signaling pathway that can regulate DNA damage checkpoint recovery and implicates the Ras signaling pathway as an important regulator of mitotic events. ..
  42. Eldridge A, Halsey W, Wuttke D. Identification of the determinants for the specific recognition of single-strand telomeric DNA by Cdc13. Biochemistry. 2006;45:871-9 pubmed
    ..The telomere end-binding proteins, Cdc13 in Saccharomyces cerevisiae, Pot1 in higher eukaryotes, and TEBP in the ciliated protozoan Oxytricha nova, exhibit ..
  43. Lazzaro F, Sapountzi V, Granata M, Pellicioli A, Vaze M, Haber J, et al. Histone methyltransferase Dot1 and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres. EMBO J. 2008;27:1502-12 pubmed publisher
  44. Nugent C, Hughes T, Lue N, Lundblad V. Cdc13p: a single-strand telomeric DNA-binding protein with a dual role in yeast telomere maintenance. Science. 1996;274:249-52 pubmed
    The CDC13 gene has previously been implicated in the maintenance of telomere integrity in Saccharomyces cerevisiae. With the use of two classes of mutations, here it is shown that CDC13 has two discrete roles at the telomere...
  45. Blankley R, Lydall D. A domain of Rad9 specifically required for activation of Chk1 in budding yeast. J Cell Sci. 2004;117:601-8 pubmed
    ..The Chk1 activation domain (CAD) of Rad9 is specifically important for signalling cell-cycle arrest after cdc13-1- and yku70Delta-induced telomere damage but not for tolerating ultraviolet-induced damage or inhibiting nuclease ..
  46. Wang Y, Hu F, Elledge S. The Bfa1/Bub2 GAP complex comprises a universal checkpoint required to prevent mitotic exit. Curr Biol. 2000;10:1379-82 pubmed
    ..b>cdc13-1 bub2 and cdc13-1 bfa1 but not cdc13-1 mad2 double mutants rebud and reduplicate their DNA at the restrictive ..
  47. Vega L, Phillips J, Thornton B, Benanti J, Onigbanjo M, Toczyski D, et al. Sensitivity of yeast strains with long G-tails to levels of telomere-bound telomerase. PLoS Genet. 2007;3:e105 pubmed
    ..a non-cell cycle-regulated promoter dramatically reduced viability in five strains with impaired end protection (cdc13-1, yku80Delta, yku70Delta, yku80-1, and yku80-4), all of which have longer single-strand G-tails than wild-type ..
  48. Hu F, Wang Y, Liu D, Li Y, Qin J, Elledge S. Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints. Cell. 2001;107:655-65 pubmed
    ..DNA damage does not inhibit Bfa1 phosphorylation and instead causes a Rad53- and Dun1-dependent modification of Bfa1. Regulation of Bfa1 may therefore be a key step controlled by multiple checkpoint pathways to ensure a mitotic arrest. ..
  49. Chandra A, Hughes T, Nugent C, Lundblad V. Cdc13 both positively and negatively regulates telomere replication. Genes Dev. 2001;15:404-14 pubmed
    b>Cdc13 is a single-strand telomeric DNA-binding protein that positively regulates yeast telomere replication by recruiting telomerase to chromosome termini through a site on Cdc13 that is eliminated by the cdc13-2 mutation...
  50. Gardner R, Putnam C, Weinert T. RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in budding yeast. EMBO J. 1999;18:3173-85 pubmed
    ..Each pathway independently contributes approximately 50% to G2/M arrest, effects demonstrable after cdc13-induced damage or a double-stranded break inflicted by the HO endonuclease...
  51. Foster S, Zubko M, Guillard S, Lydall D. MRX protects telomeric DNA at uncapped telomeres of budding yeast cdc13-1 mutants. DNA Repair (Amst). 2006;5:840-51 pubmed
    ..To investigate the role of MRX, we generated a conditionally degradable Rad50 protein and combined this with cdc13-1, a temperature sensitive mutation in the Cdc13 telomere capping protein...
  52. Xu L, Petreaca R, Gasparyan H, Vu S, Nugent C. TEN1 is essential for CDC13-mediated telomere capping. Genetics. 2009;183:793-810 pubmed publisher
    ..In Saccharomyces cerevisiae, Cdc13 binds single-stranded G-rich telomere repeats, maintaining telomere integrity and length...
  53. Liu J, He M, Peng J, Duan Y, Lu Y, Wu Z, et al. Tethering telomerase to telomeres increases genome instability and promotes chronological aging in yeast. Aging (Albany NY). 2016;8:2827-2847 pubmed publisher
    ..It remains elusive whether dysregulated telomerase activity affects chronological aging. We employed the CDC13-EST2 fusion gene, which tethers telomerase to telomeres, to examine the effect of constitutively active ..
  54. Paschini M, Mandell E, Lundblad V. Structure prediction-driven genetics in Saccharomyces cerevisiae identifies an interface between the t-RPA proteins Stn1 and Ten1. Genetics. 2010;185:11-21 pubmed publisher
    In Saccharomyces cerevisiae, Cdc13, Stn1, and Ten1 are essential for both chromosome capping and telomere length homeostasis...