{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:32:10Z","timestamp":1791117130976,"version":"4.1.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,4,24]]},"abstract":"<jats:p>\n                    Ig class switch recombination (CSR) and somatic hypermutation serve to diversify antibody responses and are orchestrated by the activity of activation-induced cytidine deaminase and many proteins involved in DNA repair and genome surveillance.\n                    <jats:italic>Msh5<\/jats:italic>\n                    , a gene encoded in the central MHC class III region, and its obligate heterodimerization partner Msh4 have a critical role in regulating meiotic homologous recombination and have not been implicated in CSR. Here, we show that MRL\/\n                    <jats:italic>lpr<\/jats:italic>\n                    mice carrying a congenic H-2\n                    <jats:sup>b\/b<\/jats:sup>\n                    MHC interval exhibit several abnormalities regarding CSR, including a profound deficiency of IgG3 in most mice and long microhomologies at Ig switch (S) joints. We found that\n                    <jats:italic>Msh5<\/jats:italic>\n                    is expressed at low levels on the H-2\n                    <jats:sup>b<\/jats:sup>\n                    haplotype and, importantly, a similar long S joint microhomology phenotype was observed in both\n                    <jats:italic>Msh5<\/jats:italic>\n                    and\n                    <jats:italic>Msh4<\/jats:italic>\n                    -null mice. We also present evidence that genetic variation in\n                    <jats:italic>MSH5<\/jats:italic>\n                    is associated with IgA deficiency and common variable immune deficiency (CVID) in humans. One of the human\n                    <jats:italic>MSH5<\/jats:italic>\n                    alleles identified contains two nonsynonymous polymorphisms, and the variant protein encoded by this allele shows impaired binding to MSH4. Similar to the mice, Ig S joints from CVID and IgA deficiency patients carrying disease-associated\n                    <jats:italic>MSH5<\/jats:italic>\n                    alleles show increased donor\/acceptor microhomology, involving pentameric DNA repeat sequences and lower mutation rates than controls. Our findings suggest that Msh4\/5 heterodimers contribute to CSR and support a model whereby Msh4\/5 promotes the resolution of DNA breaks with low or no terminal microhomology by a classical nonhomologous end-joining mechanism while possibly suppressing an alternative microhomology-mediated pathway.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0700815104","type":"journal-article","created":{"date-parts":[[2007,4,4]],"date-time":"2007-04-04T20:25:17Z","timestamp":1175718317000},"page":"7193-7198","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":127,"title":["Role for Msh5 in the regulation of Ig class switch recombination"],"prefix":"10.1073","volume":"104","author":[{"given":"Hideharu","family":"Sekine","sequence":"first","affiliation":[{"name":"Medical University of South Carolina, Charleston, SC 29425;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo C.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"University of Minnesota Medical School, Minneapolis, MN 55455;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Pan-Hammarstr\u00f6m","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital, SE-141 86 Huddinge, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Graham","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Ziemba","sequence":"additional","affiliation":[{"name":"University of Minnesota Medical School, Minneapolis, MN 55455;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra S.","family":"de Vries","sequence":"additional","affiliation":[{"name":"The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabin","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Minnesota Medical School, Minneapolis, MN 55455;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keli","family":"Hippen","sequence":"additional","affiliation":[{"name":"University of Minnesota Medical School, Minneapolis, MN 55455;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thearith","family":"Koeuth","sequence":"additional","affiliation":[{"name":"University of Minnesota Medical School, Minneapolis, MN 55455;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ward","family":"Ortmann","sequence":"additional","affiliation":[{"name":"University of Minnesota Medical School, Minneapolis, MN 55455;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Iwahori","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina, Charleston, SC 29425;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret K.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina, Charleston, SC 29425;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Offer","sequence":"additional","affiliation":[{"name":"University of Minnesota Medical School, Minneapolis, MN 55455;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara","family":"Skon","sequence":"additional","affiliation":[{"name":"University of Minnesota Medical School, Minneapolis, MN 55455;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Likun","family":"Du","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital, SE-141 86 Huddinge, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Novitzke","sequence":"additional","affiliation":[{"name":"University of Minnesota Medical School, 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