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CDC13  -  Cdc13p

Saccharomyces cerevisiae S288c

Synonyms: Cell division control protein 13, YDL220C
 
 
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Disease relevance of CDC13

 

High impact information on CDC13

 

Biological context of CDC13

  • These results suggest that the CDC13 product functions in telomere metabolism, either in the replication of telomeric DNA or in protecting telomeres from the double-strand break repair system [6].
  • Although CDC13 is an essential telomerase component in vivo, no replicative senescence can be observed in cdc13-4 cells [7].
  • Mutations in CDC13 have previously been found to cause cell cycle arrest of Saccharomyces cerevisiae at a stage in G2 immediately preceding the mitotic division [8].
  • STM1, a gene which encodes a guanine quadruplex binding protein, interacts with CDC13 in Saccharomyces cerevisiae [9].
  • Temperature-sensitive mutations in CDC13 and STN1, which are both essential genes, activate a DNA damage-dependent checkpoint which is the cause of the arrest seen in the mutant strains [10].
 

Anatomical context of CDC13

  • In the current study, we show that inactivation of Cdc13p induces apoptotic signals in yeast, as evidenced by caspase activation, increased reactive oxygen species production, and flipping of phosphatidylserine in the cytoplasmic membrane [11].
 

Associations of CDC13 with chemical compounds

 

Physical interactions of CDC13

  • It has been proposed that Cdc13p DNA binding directs a Cdc13p-Stn1p-Ten1p complex to telomeres to mediate end protection [13].
  • Cdc13 interacts with Est1 and DNA polymerase alpha, and cells carrying the temperature-sensitive allele cdc13-1 cannot complete telomere replication at the restrictive temperature and possess long telomeres [9].
  • Similarly, Est2 binding to the DSB also required the Cdc13-Est1 interaction, but not synthesis of new TG repeats at the break site [14].
  • Among the budding yeasts this conserved Cdc13p binding site overlaps the Rap1p binding site [15].
  • Pol1p was shown to interact with Cdc13p [16].
 

Regulatory relationships of CDC13

  • We propose that accurate regulation of telomerase recruitment by Cdc13 results from a coordinated balance between positive control by yKu70 and negative control by Stn1 [17].
  • Thus, Stn1p and Ten1p control a Cdc13p-independent telomere capping mechanism that is coupled to the conventional DNA replication machinery [13].
  • Inactivation of Cdc13p triggers MEC1-dependent apoptotic signals in yeast [11].
  • A RAD9-dependent checkpoint blocks meiosis of cdc13 yeast cells [8].
  • 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 [18].
 

Other interactions of CDC13

  • Chromosome end protection plasticity revealed by Stn1p and Ten1p bypass of Cdc13p [13].
  • Expression of a Cdc13-yKu70 fusion protein resulted in telomere elongation, similar to that produced by a Cdc13-Est1 fusion, thus suggesting that yKu70 might promote Cdc13-mediated telomerase recruitment [17].
  • New function of CDC13 in positive telomere length regulation [7].
  • In a synthetic lethality screen with YKU70, the 70-kDa subunit of the telomere-associated Yku heterodimer, we identified a new mutation in CDC13, cdc13-4, that points toward an additional regulatory function of CDC13 [7].
  • As predicted for a telomerase subunit, fusion of Est3p to the high affinity Cdc13p telomeric DNA binding domain greatly increases access of telomerase to the telomere [19].
 

Analytical, diagnostic and therapeutic context of CDC13

References

  1. The Saccharomyces CDC13 protein is a single-strand TG1-3 telomeric DNA-binding protein in vitro that affects telomere behavior in vivo. Lin, J.J., Zakian, V.A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  2. A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator. Downey, M., Houlsworth, R., Maringele, L., Rollie, A., Brehme, M., Galicia, S., Guillard, S., Partington, M., Zubko, M.K., Krogan, N.J., Emili, A., Greenblatt, J.F., Harrington, L., Lydall, D., Durocher, D. Cell (2006) [Pubmed]
  3. RPA regulates telomerase action by providing Est1p access to chromosome ends. Schramke, V., Luciano, P., Brevet, V., Guillot, S., Corda, Y., Longhese, M.P., Gilson, E., Géli, V. Nat. Genet. (2004) [Pubmed]
  4. Cdc13 delivers separate complexes to the telomere for end protection and replication. Pennock, E., Buckley, K., Lundblad, V. Cell (2001) [Pubmed]
  5. Est1 and Cdc13 as comediators of telomerase access. Evans, S.K., Lundblad, V. Science (1999) [Pubmed]
  6. Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Garvik, B., Carson, M., Hartwell, L. Mol. Cell. Biol. (1995) [Pubmed]
  7. New function of CDC13 in positive telomere length regulation. Meier, B., Driller, L., Jaklin, S., Feldmann, H.M. Mol. Cell. Biol. (2001) [Pubmed]
  8. A RAD9-dependent checkpoint blocks meiosis of cdc13 yeast cells. Weber, L., Byers, B. Genetics (1992) [Pubmed]
  9. STM1, a gene which encodes a guanine quadruplex binding protein, interacts with CDC13 in Saccharomyces cerevisiae. Hayashi, N., Murakami, S. Mol. Genet. Genomics (2002) [Pubmed]
  10. Hsp90 levels affect telomere length in yeast. Grandin, N., Charbonneau, M. Mol. Genet. Genomics (2001) [Pubmed]
  11. Inactivation of Cdc13p triggers MEC1-dependent apoptotic signals in yeast. Qi, H., Li, T.K., Kuo, D., Nur-E-Kamal, A., Liu, L.F. J. Biol. Chem. (2003) [Pubmed]
  12. Nif1, a novel mitotic inhibitor in Schizosaccharomyces pombe. Wu, L., Russell, P. EMBO J. (1997) [Pubmed]
  13. Chromosome end protection plasticity revealed by Stn1p and Ten1p bypass of Cdc13p. Petreaca, R.C., Chiu, H.C., Eckelhoefer, H.A., Chuang, C., Xu, L., Nugent, C.I. Nat. Cell Biol. (2006) [Pubmed]
  14. Delivery of yeast telomerase to a DNA break depends on the recruitment functions of Cdc13 and Est1. Bianchi, A., Negrini, S., Shore, D. Mol. Cell (2004) [Pubmed]
  15. Characterization of the DNA binding features of Saccharomyces castellii Cdc13p. Rhodin, J., Astromskas, E., Cohn, M. J. Mol. Biol. (2006) [Pubmed]
  16. Interaction of Saccharomyces Cdc13p with Pol1p, Imp4p, Sir4p and Zds2p is involved in telomere replication, telomere maintenance and cell growth control. Hsu, C.L., Chen, Y.S., Tsai, S.Y., Tu, P.J., Wang, M.J., Lin, J.J. Nucleic Acids Res. (2004) [Pubmed]
  17. Cdc13 cooperates with the yeast Ku proteins and Stn1 to regulate telomerase recruitment. Grandin, N., Damon, C., Charbonneau, M. Mol. Cell. Biol. (2000) [Pubmed]
  18. RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in budding yeast. Gardner, R., Putnam, C.W., Weinert, T. EMBO J. (1999) [Pubmed]
  19. The Est3 protein is a subunit of yeast telomerase. Hughes, T.R., Evans, S.K., Weilbaecher, R.G., Lundblad, V. Curr. Biol. (2000) [Pubmed]
  20. Site-directed mutagenesis reveals the thermodynamic requirements for single-stranded DNA recognition by the telomere-binding protein Cdc13. Anderson, E.M., Halsey, W.A., Wuttke, D.S. Biochemistry (2003) [Pubmed]
  21. Telomere-binding and Stn1p-interacting activities are required for the essential function of Saccharomyces cerevisiae Cdc13p. Wang, M.J., Lin, Y.C., Pang, T.L., Lee, J.M., Chou, C.C., Lin, J.J. Nucleic Acids Res. (2000) [Pubmed]
 
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