title: Mismatch repair, but not heteroduplex rejection, is temporally coupled to DNA replication.
abstract: In eukaryotes, it is unknown whether mismatch repair (MMR) is temporally coupled to DNA replication and how strand-specific MMR is directed. We fused Saccharomyces cerevisiae MSH6 with cyclins to restrict the availability of the Msh2-Msh6 mismatch recognition complex to either S phase or G2/M phase of the cell cycle. The Msh6-S cyclin fusion was proficient for suppressing mutations at three loci that replicate at mid-S phase, whereas the Msh6-G2/M cyclin fusion was defective. However, the Msh6-G2/M cyclin fusion was functional for MMR at a very late-replicating region of the genome. In contrast, the heteroduplex rejection function of MMR during recombination was partially functional during both S phase and G2/M phase. These results indicate a temporal coupling of MMR, but not heteroduplex rejection, to DNA replication.
authors.affiliation: Ludwig Institute for Cancer Research, Departments of Medicine and Cellular and Molecular Medicine and Cancer Center, Moores-UCSD Cancer Center, University of California School of Medicine-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0669, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Hombauer
authors.forename: Anjana
authors.initials: A
authors.lastname: Srivatsan
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Putnam
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kolodner
mesh_terms: D002455:Cell Division; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D053843:DNA Mismatch Repair; D004261:DNA Replication; D004271:DNA, Fungal / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016368:Frameshift Mutation; D016195:G2 Phase; D005800:Genes, Fungal; D009154:Mutation; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C093749:CLB2 protein, S cerevisiae; C095227:CLB6 protein, S cerevisiae; D019926:Cyclin B; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D009692:Nucleic Acid Heteroduplexes; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins