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    DNA damage checkpoint and recombinational repair are both important for cell survival of replication stress. Because these two processes influence each other, isolation of their respective contributions is challenging. Research in budding yeast shows that removal of the DNA helicase Mph1 improves survival of cells with defective Smc5/6 complex under replication stress. mph1 is known to reduce the levels of recombination intermediates in smc6 mutants. Here, we show that mph1 also hyperactivates the Mec1 checkpoint. We dissect the effects of recombination regulation and checkpoint hyperactivation by altering the checkpoint circuitry to enhance checkpoint signaling without reducing recombination intermediate levels. We show that these approaches, similar to mph1, lead to better survival of smc6 cells upon transient replication stress, likely by ameliorating replication and chromosomal segregation defects. Unlike mph1, however, they do not suppress smc6 sensitivity to chronic stress. Conversely, reducing the checkpoint response does not impair survival of smc6 mph1 mutants under chronic stress. These results suggest a two-phase model in which smc6 mutant survival upon transient replication stress can be improved by enhancing Mec1 checkpoint signaling, whereas smc6 sensitivity to chronic stress can be overcome by reducing recombination intermediates.

    Citation

    Yu-Hung Chen, Barnabas Szakal, Federica Castellucci, Dana Branzei, Xiaolan Zhao. DNA damage checkpoint and recombinational repair differentially affect the replication stress tolerance of Smc6 mutants. Molecular biology of the cell. 2013 Aug;24(15):2431-41

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    PMID: 23783034

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