title: The MRE11-RAD50-XRS2 complex, in addition to other non-homologous end-joining factors, is required for V(D)J joining in yeast.
abstract: Lymphoid cells of the vertebrate immune system rely on factors in the non-homologous end-joining (NHEJ) DNA repair pathway to form signal joints during V(D)J recombination. Unlike other end-joining reactions, signal joint formation is a specialized case of NHEJ that also requires the lymphoid-specific RAG proteins. Whether V(D)J recombination requires the Mre11-Rad50-Nbs1 complex remains an open question, as null mutations in any member of the complex are lethal in mammals. However, Saccharomyces cerevisiae strains carrying null mutations in components of the homologous Mre11p-Rad50p-Xrs2p (MRX) complex are viable. We therefore took advantage of a recently developed V(D)J recombination assay in yeast to assess the role of MRX in V(D)J joining. Here we confirmed that signal joint formation in yeast is dependent on the same NHEJ factors known to be required in mammalian cells. In addition, we showed an absolute requirement for the MRX complex in signal joining, suggesting that the Mre11-Rad50-Nbs1 complex may be required for signal joint formation in mammalian cells as well.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Clatworthy
authors.forename: Maria A
authors.initials: MA
authors.lastname: Valencia-Burton
authors.forename: James E
authors.initials: JE
authors.lastname: Haber
authors.forename: Marjorie A
authors.initials: MA
authors.lastname: Oettinger
mesh_terms: D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000502:physiology*; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000502:physiology*; D005803:Genes, Immunoglobulin; D019672:Genes, T-Cell Receptor; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D045567:VDJ Recombinases / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C086930:RAD50 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C086929:XRS2 protein, S cerevisiae; D045567:VDJ Recombinases; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae