Mph1 and Mus81-Mms4 Prevent Aberrant Processing of Mitotic Recombination Intermediates

作者：Mazon Gerard; Symington Lorraine S^*

来源：Molecular Cell, 2013, 52(1): 63-74.

DOI：10.1016/j.molcel.2013.09.007

Homology-dependent repair of double-strand breaks (DSBs) from nonsister templates has the potential to generate loss of heterozygosity or genome rearrangements. Here we show that the Saccharomyces cerevisiae Mph1 helicase prevents crossovers between ectopic sequences by removing substrates for Mus81-Mms4 or Rad1-Rad10 cleavage. A role for Yen1 is only apparent in the absence of Mus81. Cells lacking Mph1 and the three nucleases are highly defective in the repair of a single DSB, suggesting that the recombination intermediates that accumulate cannot be processed by the Sgs1-Top3-Rmi1 complex (STR). Consistent with this hypothesis, ectopic joint molecules (JMs) accumulate transiently in the mph1 Delta mutant and persistently when Mus81 is eliminated. Furthermore, the ectopic JMs formed in the mus81 Delta mutant contain a single Holliday junction (HJ) explaining why STR is unable to process them. We suggest that Mph1 and Mus81-Mms4 recognize an early strand exchange intermediate and direct repair to noncrossover or crossover outcomes, respectively.

• 出版日期2013-10-10