Binding of Multiple Rap1 Proteins Stimulates Chromosome Breakage Induction during DNA Replication |
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| Authors: | Greicy H. Goto Sevil Zencir Yukinori Hirano Hiroo Ogi Andreas Ivessa Katsunori Sugimoto |
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| Affiliation: | 1Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America;2Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America;Chinese Academy of Sciences, CHINA |
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| Abstract: | Telomeres, the ends of linear eukaryotic chromosomes, have a specialized chromatin structure that provides a stable chromosomal terminus. In budding yeast Rap1 protein binds to telomeric TG repeat and negatively regulates telomere length. Here we show that binding of multiple Rap1 proteins stimulates DNA double-stranded break (DSB) induction at both telomeric and non-telomeric regions. Consistent with the role of DSB induction, Rap1 stimulates nearby recombination events in a dosage-dependent manner. Rap1 recruits Rif1 and Rif2 to telomeres, but neither Rif1 nor Rif2 is required for DSB induction. Rap1-mediated DSB induction involves replication fork progression but inactivation of checkpoint kinase Mec1 does not affect DSB induction. Rap1 tethering shortens artificially elongated telomeres in parallel with telomerase inhibition, and this telomere shortening does not require homologous recombination. These results suggest that Rap1 contributes to telomere homeostasis by promoting chromosome breakage. |
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