Suppression of Chromosome Healing and Anticheckpoint Pathways in Yeast Postsenescence Survivors |
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Authors: | Xianning Lai J?rg Heierhorst |
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Affiliation: | St. Vincent’s Institute of Medical Research, Fitzroy, Victoria 3065, Australia, and Department of Medicine, St. Vincent’s Hospital, The University of Melbourne, Fitzroy, Victoria 3065, Australia |
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Abstract: | Telomere repeat-like sequences at DNA double-strand breaks (DSBs) inhibit DNA damage signaling and serve as seeds to convert DSBs to new telomeres in mutagenic chromosome healing pathways. We find here that the response to seed-containing DSBs differs fundamentally between budding yeast (Saccharomyces cerevisiae) cells that maintain their telomeres via telomerase and so-called postsenescence survivors that use recombination-based alternative lengthening of telomere (ALT) mechanisms. Whereas telomere seeds are efficiently elongated by telomerase, they remain remarkably stable without de novo telomerization or extensive end resection in telomerase-deficient (est2Δ, tlc1Δ) postsenescence survivors. This telomere seed hyper-stability in ALT cells is associated with, but not caused by, prolonged DNA damage checkpoint activity (RAD9, RAD53) compared to telomerase-positive cells or presenescent telomerase-negative cells. The results indicate that both chromosome healing and anticheckpoint activity of telomere seeds are suppressed in yeast models of ALT pathways. |
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Keywords: | ALT Rad53 Rad9 Est2 TLC1 |
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