PMID- 24119400 OWN - NLM STAT- MEDLINE DCOM- 20131206 LR - 20211021 IS - 1097-4164 (Electronic) IS - 1097-2765 (Print) IS - 1097-2765 (Linking) VI - 52 IP - 1 DP - 2013 Oct 10 TI - Mph1 and Mus81-Mms4 prevent aberrant processing of mitotic recombination intermediates. PG - 63-74 LID - S1097-2765(13)00677-1 [pii] LID - 10.1016/j.molcel.2013.09.007 [doi] AB - 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 mph1Delta mutant and persistently when Mus81 is eliminated. Furthermore, the ectopic JMs formed in the mus81Delta 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. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Mazon, Gerard AU - Mazon G AD - Department of Microbiology & Immunology, Columbia University Medical Center, New York, NY 10032, USA. FAU - Symington, Lorraine S AU - Symington LS LA - eng GR - R01 GM041784/GM/NIGMS NIH HHS/United States GR - R01 GM094386/GM/NIGMS NIH HHS/United States GR - GM041784/GM/NIGMS NIH HHS/United States GR - GM094386/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Mol Cell JT - Molecular cell JID - 9802571 RN - 0 (DNA-Binding Proteins) RN - 0 (Saccharomyces cerevisiae Proteins) RN - EC 3.1.- (Endonucleases) RN - EC 3.1.- (Flap Endonucleases) RN - EC 3.1.- (MUS81 protein, S cerevisiae) RN - EC 3.1.- (RAD1 protein, S cerevisiae) RN - EC 3.1.21.- (Holliday Junction Resolvases) RN - EC 3.1.21.- (Yen1 protein, S cerevisiae) RN - EC 3.1.22.- (MMS4 protein, S cerevisiae) RN - EC 3.1.30.1 (RAD10 protein, S cerevisiae) RN - EC 3.1.30.1 (Single-Strand Specific DNA and RNA Endonucleases) RN - EC 3.6.1.- (MPH1 protein, S cerevisiae) RN - EC 3.6.1.- (SGS1 protein, S cerevisiae) RN - EC 3.6.4.12 (RecQ Helicases) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) RN - EC 6.5.1.- (DNA Repair Enzymes) SB - IM MH - DEAD-box RNA Helicases/genetics/*metabolism MH - DNA Breaks, Double-Stranded MH - DNA Repair MH - DNA Repair Enzymes/metabolism MH - DNA-Binding Proteins/genetics/*metabolism MH - Endonucleases/genetics/*metabolism MH - Flap Endonucleases/genetics/*metabolism MH - Gene Expression Regulation, Fungal MH - Holliday Junction Resolvases/metabolism MH - *Mitosis MH - Mutation MH - RecQ Helicases/metabolism MH - *Recombination, Genetic MH - Saccharomyces cerevisiae/*enzymology/genetics MH - Saccharomyces cerevisiae Proteins/genetics/*metabolism MH - Single-Strand Specific DNA and RNA Endonucleases/metabolism MH - Time Factors PMC - PMC3818723 MID - NIHMS524419 EDAT- 2013/10/15 06:00 MHDA- 2013/12/16 06:00 PMCR- 2014/10/10 CRDT- 2013/10/15 06:00 PHST- 2013/02/27 00:00 [received] PHST- 2013/06/13 00:00 [revised] PHST- 2013/08/23 00:00 [accepted] PHST- 2013/10/15 06:00 [entrez] PHST- 2013/10/15 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] PHST- 2014/10/10 00:00 [pmc-release] AID - S1097-2765(13)00677-1 [pii] AID - 10.1016/j.molcel.2013.09.007 [doi] PST - ppublish SO - Mol Cell. 2013 Oct 10;52(1):63-74. doi: 10.1016/j.molcel.2013.09.007.