{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:33:25Z","timestamp":1791239605470,"version":"4.1.0"},"reference-count":56,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,4,5]]},"abstract":"<jats:p>Activation-induced cytosine deaminase preferentially deaminates C in DNA on the nontranscribed strand in vitro, which theoretically should produce a large increase in mutations of C during hypermutation of immunoglobulin genes. However, a bias for C mutations has not been observed among the mutations in variable genes. Therefore, we examined mutations in the \u03bc and \u03b3 switch regions, which can form stable secondary structures, to look for C mutations. To further simplify the pattern, mutations were studied in the absence of DNA polymerase (pol) \u03b7, which may produce substitutions of nucleotides downstream of C. DNA from lymphocytes of patients with xeroderma pigmentosum variant (XP-V) disease, whose polymerase \u03b7 is defective, had the same frequency of switching to all four \u03b3 isotypes and hypermutation in \u03bc-\u03b3 switch sites (0.5% mutations per basepair) as control subjects. There were fewer mutations of A and T bases in the XP-V clones, similar to variable gene mutations from these patients, which confirms that polymerase \u03b7 produces substitutions opposite A and T. Most importantly, the absence of polymerase \u03b7 revealed an increase in C mutations on the nontranscribed strand. This data shows for the first time that C is preferentially mutated in vivo and pol \u03b7 generates hypermutation in the \u03bc and \u03b3 switch regions.<\/jats:p>","DOI":"10.1084\/jem.20032022","type":"journal-article","created":{"date-parts":[[2004,3,30]],"date-time":"2004-03-30T01:54:02Z","timestamp":1080611642000},"page":"917-924","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["Absence of DNA Polymerase \u03b7 Reveals Targeting of C Mutations on the Nontranscribed Strand in Immunoglobulin Switch Regions"],"prefix":"10.1084","volume":"199","author":[{"given":"Xianmin","family":"Zeng","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Negrete","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Kasmer","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J.","family":"Gearhart","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2004,3,29]]},"reference":[{"key":"2023072512275929600_BIB1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0092-8674(00)00078-7","volume":"102","year":"2000","journal-title":"Cell."},{"key":"2023072512275929600_BIB2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0092-8674(00)00079-9","volume":"102","year":"2000","journal-title":"Cell."},{"key":"2023072512275929600_BIB3","first-page":"99","volume":"418","year":"2002","journal-title":"Nature."},{"key":"2023072512275929600_BIB4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature00981","volume":"419","year":"2002","journal-title":"Nature."},{"key":"2023072512275929600_BIB5","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1016\/S0960-9822(02)01215-0","volume":"12","year":"2002","journal-title":"Curr. 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