title: Role of RAD51C and XRCC3 in genetic recombination and DNA repair.
abstract: In germ line cells, recombination is required for gene reassortment and proper chromosome segregation at meiosis, whereas in somatic cells it provides an important mechanism for the repair of DNA double-strand breaks. Five proteins (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) that share homology with RAD51 recombinase and are known as the RAD51 paralogs are important for recombinational repair, as paralog-defective cell lines exhibit spontaneous chromosomal aberrations, defective DNA repair, and reduced gene targeting. The paralogs form two distinct protein complexes, RAD51B-RAD51C-RAD51D-XRCC2 and RAD51C-XRCC3, but their precise cellular roles remain unknown. Here, we show that, like MLH1, RAD51C localized to mouse meiotic chromosomes at pachytene/diplotene. Using immunoprecipitation and gel filtration analyses, we found that Holliday junction resolvase activity associated tightly and co-eluted with the 80-kDa RAD51C-XRCC3 complex. Taken together, these data indicate that the RAD51C-XRCC3-associated Holliday junction resolvase complex associates with crossovers and may play an essential role in the resolution of recombination intermediates prior to chromosome segregation.
authors.affiliation: Clare Hall Laboratories, London Research Institute, Cancer Research UK, South Mimms, Hertfordshire EN6 3LD, United Kingdom.
authors.forename: Yilun
authors.initials: Y
authors.lastname: Liu
authors.forename: Madalena
authors.initials: M
authors.lastname: Tarsounas
authors.forename: Paul
authors.initials: P
authors.lastname: O'regan
authors.forename: Stephen C
authors.initials: SC
authors.lastname: West
mesh_terms: D000818:Animals; D002465:Cell Movement; D047369:Chromatin Immunoprecipitation; D002850:Chromatography, Gel; D002869:Chromosome Aberrations; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D011485:Protein Binding; D011995:Recombination, Genetic
chemical_list: D004268:DNA-Binding Proteins; C448305:RAD51C protein, human; C110901:X-ray repair cross complementing protein 3