PMID- 22696213 OWN - NLM STAT- MEDLINE DCOM- 20121105 LR - 20220129 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 287 IP - 32 DP - 2012 Aug 3 TI - Rad5-dependent DNA repair functions of the Saccharomyces cerevisiae FANCM protein homolog Mph1. PG - 26563-75 LID - 10.1074/jbc.M112.369918 [doi] AB - Interstrand cross-links (ICLs) covalently link complementary DNA strands, block DNA replication, and transcription and must be removed to allow cell survival. Several pathways, including the Fanconi anemia (FA) pathway, can faithfully repair ICLs and maintain genomic integrity; however, the precise mechanisms of most ICL repair processes remain enigmatic. In this study we genetically characterized a conserved yeast ICL repair pathway composed of the yeast homologs (Mph1, Chl1, Mhf1, Mhf2) of four FA proteins (FANCM, FANCJ, MHF1, MHF2). This pathway is epistatic with Rad5-mediated DNA damage bypass and distinct from the ICL repair pathways mediated by Rad18 and Pso2. In addition, consistent with the FANCM role in stabilizing ICL-stalled replication forks, we present evidence that Mph1 prevents ICL-stalled replication forks from collapsing into double-strand breaks. This unique repair function of Mph1 is specific for ICL damage and does not extend to other types of damage. These studies reveal the functional conservation of the FA pathway and validate the yeast model for future studies to further elucidate the mechanism of the FA pathway. FAU - Daee, Danielle L AU - Daee DL AD - Genome Instability Section, Genetics, and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA FAU - Ferrari, Elisa AU - Ferrari E FAU - Longerich, Simonne AU - Longerich S FAU - Zheng, Xiao-feng AU - Zheng XF FAU - Xue, Xiaoyu AU - Xue X FAU - Branzei, Dana AU - Branzei D FAU - Sung, Patrick AU - Sung P FAU - Myung, Kyungjae AU - Myung K LA - eng GR - 242928/ERC_/European Research Council/International GR - Z01 HG012003/ImNIH/Intramural NIH HHS/United States GR - HG012003-09/HG/NHGRI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120612 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Saccharomyces cerevisiae Proteins) RN - EC 3.6.1.- (FANCM protein, human) RN - EC 3.6.1.- (MPH1 protein, S cerevisiae) RN - EC 3.6.1.- (RAD5 protein, S cerevisiae) RN - EC 3.6.4.- (DNA Helicases) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) SB - IM MH - DEAD-box RNA Helicases/genetics/*physiology MH - DNA Helicases/genetics/*physiology MH - DNA Repair/*physiology MH - Electrophoresis, Gel, Pulsed-Field MH - Flow Cytometry MH - Humans MH - Mutation MH - Saccharomyces cerevisiae/*genetics MH - Saccharomyces cerevisiae Proteins/genetics/*physiology PMC - PMC3410997 EDAT- 2012/06/15 06:00 MHDA- 2012/11/06 06:00 PMCR- 2013/08/03 CRDT- 2012/06/15 06:00 PHST- 2012/06/15 06:00 [entrez] PHST- 2012/06/15 06:00 [pubmed] PHST- 2012/11/06 06:00 [medline] PHST- 2013/08/03 00:00 [pmc-release] AID - S0021-9258(20)47853-6 [pii] AID - M112.369918 [pii] AID - 10.1074/jbc.M112.369918 [doi] PST - ppublish SO - J Biol Chem. 2012 Aug 3;287(32):26563-75. doi: 10.1074/jbc.M112.369918. Epub 2012 Jun 12.