Canonical Non-Homologous End Joining in Mitosis Induces Genome Instability and Is Suppressed by M-phase-Specific Phosphorylation of XRCC4

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DNA double-strand breaks (DSBs) are highly toxic to cells and often lead to genome instability and cell death. Organisms have several DSB repair mechanisms to prevent such instability. Proper choice of DSB repair pathways is highly regulated during the cell cycle. Inappropriate choice of the DSB repair pathway often results in perturbation or failure of DSB repair, which is occasionally associated with tumorigenesis. Although the DSB repair pathways in the cell-cycle phases G1, S, and G2 are well elucidated, little is known about how cells deal with DSBs induced during M phase. We found that M-phase DSBs trigger massive chromosome aberrations, suggesting a lack of and/or inappropriate DSB repair during M phase. Notably, DNA damage response factors do not localize to mitotic chromosomes, and DSB repair pathways seem to be largely suppressed during M phase. In this study, we show that the efficiency of DSB repair is low during mitosis rather than being completely repressed. DSB repair, which generally prevents genome instability, causes genome instability during M phase. Cells have a mechanism to suppress DSB repair during M phase to prevent genome instability by modifying a non-homologous end-joining factor that is critical for DSB repair during other cell-cycle phases.

Vyšlo v časopise: Canonical Non-Homologous End Joining in Mitosis Induces Genome Instability and Is Suppressed by M-phase-Specific Phosphorylation of XRCC4. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004563
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004563

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