Mph1 and Mus81-Mms4 prevent aberrant processing of mitotic recombination intermediates.

Abstract:

: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 mph1Δ mutant and persistently when Mus81 is eliminated. Furthermore, the ectopic JMs formed in the mus81Δ 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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Mazón G,Symington LS

doi

10.1016/j.molcel.2013.09.007

subject

Has Abstract

pub_date

2013-10-10 00:00:00

pages

63-74

issue

1

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(13)00677-1

journal_volume

52

pub_type

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