title: Homologous recombination proteins are associated with centrosomes and are required for mitotic stability.
abstract: In response to DNA damage, cells need robust repair mechanisms to complete the cell cycle successfully. Severe forms of DNA damage are repaired by homologous recombination (HR), in which the XRCC2 protein plays a vital role. Cells deficient in XRCC2 also show disruption of the centrosome, a key component of the mitotic apparatus. We find that this centrosome disruption is dynamic and when it occurs during mitosis it is linked directly to the onset of mitotic catastrophe in a significant fraction of the XRCC2-deficient cells. However, we also show for the first time that XRCC2 and other HR proteins, including the key recombinase RAD51, co-localize with the centrosome. Co-localization is maintained throughout the cell cycle, except when cells are finishing mitosis when RAD51 accumulates in the midbody between the separating cells. Taken together, these data suggest a tight functional linkage between the centrosome and HR proteins, potentially to coordinate the deployment of a DNA damage response at vulnerable phases of the cell cycle.
authors.affiliation: Medical Research Council, Radiation & Genome Stability Unit, Oxon OX11 0RD, UK.
authors.forename: Enrico
authors.initials: E
authors.lastname: Cappelli
authors.forename: Stuart
authors.initials: S
authors.lastname: Townsend
authors.forename: Carol
authors.initials: C
authors.lastname: Griffin
authors.forename: John
authors.initials: J
authors.lastname: Thacker
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism*; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D015739:Nocodazole / Q000494:pharmacology; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D004268:DNA-Binding Proteins; C112629:RAD51D protein, human; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D050257:Tubulin Modulators; C113187:XRCC2 protein, human; C491866:Xrcc2 protein, mouse; D051135:Rad51 Recombinase; D015739:Nocodazole