title: Telomerase-null survivor screening identifies novel telomere recombination regulators.
abstract: Telomeres are protein-DNA structures found at the ends of linear chromosomes and are crucial for genome integrity. Telomeric DNA length is primarily maintained by the enzyme telomerase. Cells lacking telomerase will undergo senescence when telomeres become critically short. In Saccharomyces cerevisiae, a very small percentage of cells lacking telomerase can remain viable by lengthening telomeres via two distinct homologous recombination pathways. These "survivor" cells are classified as either Type I or Type II, with each class of survivor possessing distinct telomeric DNA structures and genetic requirements. To elucidate the regulatory pathways contributing to survivor generation, we knocked out the telomerase RNA gene TLC1 in 280 telomere-length-maintenance (TLM) gene mutants and examined telomere structures in post-senescent survivors. We uncovered new functional roles for 10 genes that affect the emerging ratio of Type I versus Type II survivors and 22 genes that are required for Type II survivor generation. We further verified that Pif1 helicase was required for Type I recombination and that the INO80 chromatin remodeling complex greatly affected the emerging frequency of Type I survivors. Finally, we found the Rad6-mediated ubiquitination pathway and the KEOPS complex were required for Type II recombination. Our data provide an independent line of evidence supporting the idea that these genes play important roles in telomere dynamics.
authors: The State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
authors: Yan
authors: Y
authors: Hu
authors: Hong-Bo
authors: HB
authors: Tang
authors: Ning-Ning
authors: NN
authors: Liu
authors: Xia-Jing
authors: XJ
authors: Tong
authors: Wei
authors: W
authors: Dang
authors: Yi-Min
authors: YM
authors: Duan
authors: Xiao-Hong
authors: XH
authors: Fu
authors: Yang
authors: Y
authors: Zhang
authors: Jing
authors: J
authors: Peng
authors: Fei-Long
authors: FL
authors: Meng
authors: Jin-Qiu
authors: JQ
authors: Zhou
mesh_terms: D002875:Chromosomes / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D042822:Genomic Instability; D059765:Homologous Recombination; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics; D059505:Telomere Homeostasis / Q000235:genetics; D054875:Ubiquitination
chemical_list: D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase; C085463:PIF1 protein, S cerevisiae; D004265:DNA Helicases
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