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• W2759676893 abstract "CYREN is a direct inhibitor of classical non-homologous end joining that promotes error-free repair by homologous recombination during the S and G2 phases of the cell cycle. A broken DNA molecule can be repaired in two distinct ways: homologous recombination, or classical non-homologous end joining (cNHEJ). Both processes function in the S and G2 phases of the cell cycle, but why cNHEJ is not always used is unknown. Jan Karlseder and colleagues have found that cNHEJ is suppressed in S and G2 by CYREN (cell cycle regulator of NHEJ), which binds to the Ku complex to inhibit the initial steps of end joining. The absence of CYREN results in genomic instability. CYREN thus biases repair in S and G2, when sister chromatids are available, to a recombination process that, unlike cNHEJ, is error-free. Classical non-homologous end joining1 (cNHEJ) and homologous recombination2 compete for the repair of double-stranded DNA breaks during the cell cycle. Homologous recombination is inhibited during the G1 phase of the cell cycle, but both pathways are active in the S and G2 phases. However, it is unclear why cNHEJ does not always outcompete homologous recombination during the S and G2 phases. Here we show that CYREN (cell cycle regulator of NHEJ) is a cell-cycle-specific inhibitor of cNHEJ. Suppression of CYREN allows cNHEJ to occur at telomeres and intrachromosomal breaks during the S and G2 phases, and cells lacking CYREN accumulate chromosomal aberrations upon damage induction, specifically outside the G1 phase. CYREN acts by binding to the Ku70/80 heterodimer and preferentially inhibits cNHEJ at breaks with overhangs by protecting them. We therefore propose that CYREN is a direct cell-cycle-dependent inhibitor of cNHEJ that promotes error-free repair by homologous recombination during cell cycle phases when sister chromatids are present." @default.
• W2759676893 created "2017-10-06" @default.
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• W2759676893 date "2017-09-01" @default.
• W2759676893 modified "2023-10-11" @default.
• W2759676893 title "Regulation of DNA repair pathway choice in S and G2 phases by the NHEJ inhibitor CYREN" @default.
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• W2759676893 doi "https://doi.org/10.1038/nature24023" @default.
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