title: Fission yeast Ccq1 is telomerase recruiter and local checkpoint controller.
abstract: Telomeres recruit telomerase and differentiate chromosome ends from sites of DNA damage. Although the DNA damage checkpoint PI3-kinases ATM and ATR localize to telomeres and promote telomerase activation, activation of their downstream checkpoint pathway targets is inhibited. Here, we show that the fission yeast telomeric protein Ccq1 is required for telomerase recruitment and inhibition of ATR target activation at telomeres. The loss of Ccq1 results in progressive telomere shortening and persistent ATR-dependent activation of Chk1. Unlike the checkpoint activation that follows loss of telomerase, this checkpoint activation occurs prior to detectable levels of critically short telomeres. When ccq1Delta telomeres do become critically short, activated Chk1 promotes an unusual homologous recombination-based telomere maintenance process. We find that the previously reported meiotic segregation defects of cells lacking Ccq1 stem from its role in telomere maintenance rather than from a role in formation of the meiotic bouquet. These findings demonstrate the existence of a novel telomerase recruitment factor that also serves to suppress local checkpoint activation.
authors.affiliation: Telomere Biology Laboratory, Cancer Research UK, London WC2A 3PX, United Kingdom.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tomita
authors.forename: Julia Promisel
authors.initials: JP
authors.lastname: Cooper
mesh_terms: D000071877:Checkpoint Kinase 1; D015825:Chromosomes, Fungal / Q000378:metabolism; D018816:Genes, cdc / Q000502:physiology*; D008540:Meiosis / Q000235:genetics; D008938:Mitosis / Q000235:genetics; D011494:Protein Kinases / Q000378:metabolism; D011995:Recombination, Genetic; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism*; D017384:Sequence Deletion; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000201:enzymology / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000235:genetics
chemical_list: C529647:Ccq1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D034501:Telomere-Binding Proteins; C104344:taz1 protein, S pombe; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605873:Chk1 protein, S pombe; D019098:Telomerase