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- W2121609415 abstract "Robustness and completion of DNA replication rely on redundant DNA replication origins. Reduced efficiency of origin licensing is proposed to contribute to chromosome instability in CDK-deregulated cell cycles, a frequent alteration in oncogenesis. However, the mechanism by which this instability occurs is largely unknown. Current models suggest that limited origin numbers would reduce fork density favouring chromosome rearrangements, but experimental support in CDK-deregulated cells is lacking. We have investigated the pattern of origin firing efficiency in budding yeast cells lacking the CDK regulators Cdh1 and Sic1. We show that each regulator is required for efficient origin activity, and that both cooperate non-redundantly. Notably, origins are differentially sensitive to CDK deregulation. Origin sensitivity is independent on normal origin efficiency, firing timing or chromosomal location. Interestingly, at a chromosome arm, there is a shortage of origin firing involving active and dormant origins, and the extent of shortage correlates with the severity of CDK deregulation and chromosome instability. We therefore propose that CDK deregulation in G1 phase compromises origin redundancy by decreasing the number of active and dormant origins, leading to origin shortage and increased chromosome instability." @default.
- W2121609415 created "2016-06-24" @default.
- W2121609415 creator A5006127905 @default.
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- W2121609415 creator A5038893270 @default.
- W2121609415 creator A5059339830 @default.
- W2121609415 creator A5064457047 @default.
- W2121609415 date "2014-04-21" @default.
- W2121609415 modified "2023-09-25" @default.
- W2121609415 title "The CDK regulators Cdh1 and Sic1 promote efficient usage of DNA replication origins to prevent chromosomal instability at a chromosome arm" @default.
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- W2121609415 doi "https://doi.org/10.1093/nar/gku313" @default.
- W2121609415 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4066753" @default.
- W2121609415 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24753426" @default.
- W2121609415 hasPublicationYear "2014" @default.