title: Suppression of chromosome healing and anticheckpoint pathways in yeast postsenescence survivors.
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.
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.
authors.forename: Xianning
authors.initials: X
authors.lastname: Lai
authors.forename: Jörg
authors.initials: J
authors.lastname: Heierhorst
mesh_terms: D002453:Cell Cycle; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000235:genetics / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004271:DNA, Fungal / Q000378:metabolism*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D059505:Telomere Homeostasis; D013997:Time Factors
chemical_list: D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; C069930:rad9 protein; D064447:Checkpoint Kinase 2; C067022:RAD53 protein, S cerevisiae; C509185:EST2 protein, S cerevisiae; D019098:Telomerase
keywords: ALT; Est2; Rad53; Rad9; TLC1
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