title: Ku stabilizes replication forks in the absence of Brc1.
abstract: DNA replication errors are a major source of genome instability in all organisms. In the fission yeast Schizosaccharomyces pombe, the DNA damage response protein Brc1 binds phospho-histone H2A (γH2A)-marked chromatin during S-phase, but how Brc1 protects genome integrity remains unclear. Here we report that the non-homologous end-joining (NHEJ) protein Ku becomes critical for survival of replication stress in brc1∆ cells. Ku's protective activity in brc1∆ cells does not involve its canonical NHEJ function or its roles in protecting telomeres or shielding DNA ends from Exo1 exonuclease. In brc1∆ pku80∆ cells, nuclear foci of Rad52 homologous recombination (HR) protein increase and Mus81-Eme1 Holliday junction resolvase becomes critical, indicating increased replication fork instability. Ku's localization at a ribosomal DNA replication fork barrier associated with frequent replisome-transcriptosome collisions increases in brc1∆ cells and increased collisions correlate with an enhanced requirement for Brc1. These data indicate that Ku stabilizes replication forks in the absence of Brc1.
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Arancha
authors.initials: A
authors.lastname: Sánchez
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Russell
mesh_terms: D034961:Antigens, Nuclear / Q000378:metabolism*; D004249:DNA Damage; D059766:DNA End-Joining Repair; D004261:DNA Replication; D004271:DNA, Fungal / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D042822:Genomic Instability; D000072200:Ku Autoantigen; D016196:S Phase; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; C511286:Brc1 protein, S pombe; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; D000072200:Ku Autoantigen