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- W3080351647 abstract "Abstract Persistent DNA damage arising from unrepaired broken chromosomes or telomere loss can promote DNA damage checkpoint adaptation, and cell cycle progression, thereby increasing cell survival but also genome instability. However, the nature and extent of such instability is unclear. We show, using Schizosaccharomyces pombe , that inherited broken chromosomes, arising from failed homologous recombination repair, are subject to cycles of se gregation, DNA r eplication and extensive end- p rocessing, termed here SERPent cycles, by daughter cells, over multiple generations. Following Chk1 loss these post-adaptive cycles continue until extensive processing through inverted repeats promotes annealing, fold-back inversion and a spectrum of chromosomal rearrangements, typically isochromosomes, or chromosome loss, in the resultant population. These findings explain how persistent DNA damage drives widespread genome instability, with implications for punctuated evolution, genetic disease and tumorigenesis. One Sentence Summary Replication and processing of inherited broken chromosomes drives chromosomal instability." @default.
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- W3080351647 date "2020-08-27" @default.
- W3080351647 modified "2023-10-16" @default.
- W3080351647 title "Persistent broken chromosome inheritance drives genome instability" @default.
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- W3080351647 doi "https://doi.org/10.1101/2020.08.26.268565" @default.
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