title: Mms1-Mms22 complex protects genome integrity in Schizosaccharomyces pombe.
abstract: Mms1 and Mms22 are subunits of an Rtt101-based E3 ubiquitin ligase required for replication of damaged DNA templates in Saccharomyces cerevisiae. The function and evolutionary conservation of this DNA repair module are unknown. Here we report the characterization of an Mms1 ortholog in Schizosaccharomyces pombe. Fission yeast Mms1 was discovered through its physical association with S. pombe Mms22 (also known as Mus7). Loss of S. pombe Mms1 results in the accumulation of spontaneous DNA damage, mitotic delay, and hypersensitivity to genotoxins such as camptothecin that perturb replisome progression. Homologous recombination repair proteins Rhp51 and Rad22 (Rad51 and Rad52 orthologs, respectively) are critical for survival in the absence of Mms1; however, there is no such requirement for Mus81-Eme1 Holliday junction resolvase that is essential for recovery from broken replication forks. Mms1 and Mms22 mutants share similar phenotypes and are genetically epistatic under unperturbed growth conditions and following exposure to genotoxins. From these data we conclude that an evolutionary conserved Mms1-Mms22 complex is required for replication of damaged DNA in fission yeast.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Dovey
authors.forename: Aaron
authors.initials: A
authors.lastname: Aslanian
authors.forename: Sevil
authors.initials: S
authors.lastname: Sofueva
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Paul
authors.initials: P
authors.lastname: Russell
mesh_terms: D000595:Amino Acid Sequence; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics*; D016681:Genome, Fungal; D008969:Molecular Sequence Data; D010641:Phenotype; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; C521699:MUS7 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins