title: Elg1 forms an alternative RFC complex important for DNA replication and genome integrity.
abstract: Genome-wide synthetic genetic interaction screens with mutants in the mus81 and mms4 replication fork-processing genes identified a novel replication factor C (RFC) homolog, Elg1, which forms an alternative RFC complex with Rfc2-5. This complex is distinct from the DNA replication RFC, the DNA damage checkpoint RFC and the sister chromatid cohesion RFC. As expected from its genetic interactions, elg1 mutants are sensitive to DNA damage. Elg1 is redundant with Rad24 in the DNA damage response and contributes to activation of the checkpoint kinase Rad53. We find that elg1 mutants display DNA replication defects and genome instability, including increased recombination and mutation frequencies, and minichromosome maintenance defects. Mutants in elg1 show genetic interactions with pathways required for processing of stalled replication forks, and are defective in recovery from DNA damage during S phase. We propose that Elg1-RFC functions both in normal DNA replication and in the DNA damage response.
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bellaoui
authors.forename: Michael
authors.initials: M
authors.lastname: Chang
authors.forename: Jiongwen
authors.initials: J
authors.lastname: Ou
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
authors.forename: Grant W
authors.initials: GW
authors.lastname: Brown
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D004271:DNA, Fungal / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D016678:Genome; D006918:Hydroxyurea / Q000494:pharmacology; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010105:Oxygenases / Q000633:toxicity; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011995:Recombination, Genetic; D051818:Replication Protein C; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C477609:Elg1 protein, S cerevisiae; D009153:Mutagens; D019384:Nucleic Acid Synthesis Inhibitors; D029701:Saccharomyces cerevisiae Proteins; D010105:Oxygenases; C021555:methane monooxygenase; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D051818:Replication Protein C; D006918:Hydroxyurea