title: Fission yeast Taz1 and RPA are synergistically required to prevent rapid telomere loss.
abstract: The telomere complex must allow nucleases and helicases to process chromosome ends to make them substrates for telomerase, while preventing these same activities from disrupting chromosome end-protection. Replication protein A (RPA) binds to single-stranded DNA and is required for DNA replication, recombination, repair, and telomere maintenance. In fission yeast, the telomere binding protein Taz1 protects telomeres and negatively regulates telomerase. Here, we show that taz1-d rad11-D223Y double mutants lose their telomeric DNA, indicating that RPA (Rad11) and Taz1 are synergistically required to prevent telomere loss. Telomere loss in the taz1-d rad11-D223Y double mutants was suppressed by additional mutation of the helicase domain in a RecQ helicase (Rqh1), or by overexpression of Pot1, a single-strand telomere binding protein that is essential for protection of chromosome ends. From our results, we propose that in the absence of Taz1 and functional RPA, Pot1 cannot function properly and the helicase activity of Rqh1 promotes telomere loss. Our results suggest that controlling the activity of Rqh1 at telomeres is critical for the prevention of genomic instability.
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kibe
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Ono
authors.forename: Koichiro
authors.initials: K
authors.lastname: Sato
authors.forename: Masaru
authors.initials: M
authors.lastname: Ueno
mesh_terms: D002453:Cell Cycle; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D051716:Replication Protein A / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D000089804:Shelterin Complex; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C480031:Rad11 protein, S pombe; C480032:Rad50 protein, S pombe; D051716:Replication Protein A; D029702:Schizosaccharomyces pombe Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C499082:pot1 protein, S pombe; C104344:taz1 protein, S pombe; C509188:trt1 protein, S pombe; D019098:Telomerase; D004265:DNA Helicases; C106462:Rqh1 protein, S pombe