Cdc13 prevents telomere uncapping and Rad50-dependent homologous recombination.
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. Checkpoint-deficient cdc13-1 cells accumulated DNA damage and eventually senesced. However, these telomerase-proficient cells could survive by using homologous recombination but, contrary to telomerase-deficient cells, did so without prior telomere shortening. Strikingly, homologous recombination in cdc13-1 mec3, as well as in telomerase-deficient cdc13-1 cells, which were Rad52- and Rad50-dependent but Rad51-independent, exclusively amplified the TG(1-3) repeats. This argues that not only short telomeres are substrates for type II recombination. The Cdc13-1 mutant protein harbored a defect in its association with Stn1 and Ten1 but also an additional, unknown, defect that could not be cured by expressing a Cdc13-1- Ten1-Stn1 fusion. We propose that Cdc13 prevents telomere uncapping and inhibits recombination between telomeric sequences through a pathway distinct from and complementary to that used by telomerase.
Grandin
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N
UMR CNRS/ENS No. 5665, Ecole Normale Supérieure de Lyon, 46, allée d'Italie, 69364 Lyon, France.
Damon
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C
Charbonneau
M
M
D018797:Cell Cycle Proteins / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D018816:Genes, cdc; D009154:Mutation; D051135:Rad51 Recombinase; D051721:Rad52 DNA Repair and Recombination Protein; D011995:Recombination, Genetic / Q000502:physiology*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins; D013696:Temperature
D018797:Cell Cycle Proteins; D019926:Cyclin B; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C099938:MEC3 protein, S cerevisiae; C086930:RAD50 protein, S cerevisiae; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; C428109:Stn1 protein, S cerevisiae; D034501:Telomere-Binding Proteins; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; D019098:Telomerase