{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:33:23Z","timestamp":1791239603587,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T00:00:00Z","timestamp":1241136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Patients with the variant form of xeroderma pigmentosum (XPV) syndrome have a genetic deficiency in DNA polymerase (Pol) \u03b7, and display accordingly an increased skin sensitivity to UV light, as well as an altered mutation pattern of their Ig V genes in memory B cells, alteration that consists in a reduced mutagenesis at A\/T bases. We previously suggested that another polymerase with a different mutation signature, Pol \u03ba, is used as backup for Ig gene hypermutation in both humans and mice in cases of complete Pol \u03b7 deficiency, a proposition supported in this study by the analysis of Pol \u03b7 \u00d7 Pol \u03ba double-deficient mice. We also describe a new XPV case, in which a splice site mutation of the first noncoding exon results in a decreased mRNA expression, a mRNA that otherwise encodes a normal Pol \u03b7 protein. Whereas the Pol \u03b7 mRNA level observed in patient\u2019s fibroblasts is one-twentieth the value of healthy controls, it is only reduced to one-fourth of the normal level in activated B cells. Memory B cells from this patient showed a 50% reduction in A\/T mutations, with a spectrum that still displays a strict Pol \u03b7 signature. Pol \u03b7 thus appears as a dominant enzyme in hypermutation, its presence precluding the use of a substitute enzyme even in conditions of reduced availability. Such a dominant behavior may explain the lack of Pol \u03ba signature in Ig gene mutations of some XPV patients previously described, for whom residual Pol \u03b7 activity might exist.<\/jats:p>","DOI":"10.4049\/jimmunol.0900177","type":"journal-article","created":{"date-parts":[[2009,5,4]],"date-time":"2009-05-04T16:48:20Z","timestamp":1241455700000},"page":"6353-6359","source":"Crossref","is-referenced-by-count":39,"title":["A Backup Role of DNA Polymerase \u03ba in Ig Gene Hypermutation Only Takes Place in the Complete Absence of DNA Polymerase \u03b7"],"prefix":"10.1093","volume":"182","author":[{"given":"Ahmad","family":"Faili","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unite 783 \u201cD\u00e9veloppement du syst\u00e8me immunitaire,\u201d Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine, Site Necker-Enfants Malades , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Stary","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique FRE 2939 Stabilit\u00e9 g\u00e9n\u00e9tique et oncog\u00e9n\u00e8se, Universit\u00e9 Paris Sud, Institut Gustave Roussy , Villejuif,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Delbos","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unite 783 \u201cD\u00e9veloppement du syst\u00e8me immunitaire,\u201d Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine, Site Necker-Enfants Malades , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Weller","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unite 783 \u201cD\u00e9veloppement du syst\u00e8me immunitaire,\u201d Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine, Site Necker-Enfants Malades , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Aoufouchi","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unite 783 \u201cD\u00e9veloppement du syst\u00e8me immunitaire,\u201d Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine, Site Necker-Enfants Malades , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Sarasin","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique FRE 2939 Stabilit\u00e9 g\u00e9n\u00e9tique et oncog\u00e9n\u00e8se, Universit\u00e9 Paris Sud, Institut Gustave Roussy , Villejuif,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Claude","family":"Weill","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unite 783 \u201cD\u00e9veloppement du syst\u00e8me immunitaire,\u201d Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine, Site Necker-Enfants Malades , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude-Agn\u00e8s","family":"Reynaud","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unite 783 \u201cD\u00e9veloppement du syst\u00e8me immunitaire,\u201d Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine, Site Necker-Enfants Malades , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,5,15]]},"reference":[{"key":"2026012806314223000_R1","first-page":"553","article-title":"Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme.","volume-title":"Cell","year":"2000"},{"key":"2026012806314223000_R2","first-page":"565","article-title":"Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the hyper-IgM syndrome (HIGM2).","volume-title":"Cell","year":"2000"},{"key":"2026012806314223000_R3","first-page":"99","article-title":"AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification.","volume-title":"Nature","year":"2002"},{"key":"2026012806314223000_R4","first-page":"302","article-title":"DNA polymerases in adaptive immunity.","volume-title":"Nat. Rev. Immunol.","year":"2008"},{"key":"2026012806314223000_R5","first-page":"537","article-title":"DNA polymerase \u03b7 is an A-T mutator in somatic hypermutation of immunoglobulin variable genes.","volume-title":"Nat. Immunol.","year":"2001"},{"key":"2026012806314223000_R6","first-page":"700","article-title":"The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase \u03b7.","volume-title":"Nature","year":"1999"},{"key":"2026012806314223000_R7","first-page":"263","article-title":"hRAD30 mutations in the variant form of xeroderma pigmentosum.","volume-title":"Science","year":"1999"},{"key":"2026012806314223000_R8","first-page":"265","article-title":"DNA polymerase \u03b7 is involved in hypermutation occurring during immunoglobulin class switch recombination.","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2026012806314223000_R9","first-page":"1191","article-title":"Contribution of DNA polymerase \u03b7 to immunoglobulin gene hypermutation in the mouse.","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026012806314223000_R10","first-page":"8656","article-title":"Different mutation signatures in DNA polymerase \u03b7- and MSH6-deficient mice suggest separate roles in antibody diversification.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2005"},{"key":"2026012806314223000_R11","first-page":"17","article-title":"DNA polymerase \u03b7 is the sole contributor of A\/T modifications during immunoglobulin gene hypermutation in the mouse.","volume-title":"J. Exp. Med.","year":"2007"},{"key":"2026012806314223000_R12","first-page":"163","article-title":"Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A\/T-focused phase of somatic mutation.","volume-title":"Mol. Cell","year":"2004"},{"key":"2026012806314223000_R13","first-page":"1","article-title":"Molecular mechanisms of antibody somatic hypermutation.","volume-title":"Annu. Rev. Biochem.","year":"2007"},{"key":"2026012806314223000_R14","first-page":"613","article-title":"Competitive repair pathways in immunoglobulin gene hypermutation.","volume-title":"Philos. Trans. R. Soc. London","year":"2009"},{"key":"2026012806314223000_R15","first-page":"3152","article-title":"DNA polymerase \u03ba deficiency does not affect somatic hypermutation in mice.","volume-title":"Eur. J. Immunol.","year":"2002"},{"key":"2026012806314223000_R16","first-page":"815","article-title":"Molecular analysis of mutations in DNA polymerase \u03b7 in xeroderma pigmentosum-variant patients.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2002"},{"key":"2026012806314223000_R17","first-page":"1331","article-title":"Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+ IgD+ CD27+ B cell repertoire in infants.","volume-title":"J. Exp. Med.","year":"2008"},{"key":"2026012806314223000_R18","first-page":"39678","article-title":"Fidelity and processivity of DNA synthesis by DNA polymerase \u03ba, the product of the human DINB1 gene.","volume-title":"J. Biol. Chem.","year":"2000"},{"key":"2026012806314223000_R19","first-page":"4147","article-title":"Human DNA polymerase \u03ba synthesizes DNA with extraordinarily low fidelity.","volume-title":"Nucleic Acids Res.","year":"2000"},{"key":"2026012806314223000_R20","first-page":"267","article-title":"Human marginal zone B cells.","volume-title":"Annu. Rev. Immunol.","year":"2009"},{"key":"2026012806314223000_R21","first-page":"7781","article-title":"DNA polymerase \u03b7 contributes to strand bias of mutations of A versus T in immunoglobulin genes.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012806314223000_R22","first-page":"335","article-title":"Error rate and specificity of human and murine DNA polymerase \u03b7.","volume-title":"J. Mol. Biol.","year":"2001"},{"key":"2026012806314223000_R23","first-page":"1750","article-title":"Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes.","volume-title":"Science","year":"1998"},{"key":"2026012806314223000_R24","first-page":"11816","article-title":"BCL-6 mutations in normal germinal center B cells: evidence of somatic hypermutation acting outside Ig loci.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998"},{"key":"2026012806314223000_R25","first-page":"341","article-title":"Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas.","volume-title":"Nature","year":"2001"},{"key":"2026012806314223000_R26","first-page":"841","article-title":"Two levels of protection for the B cell genome during somatic hypermutation.","volume-title":"Nature","year":"2008"},{"key":"2026012806314223000_R27","first-page":"1949","article-title":"AID expression levels determine the extent of cMyc oncogenic translocations and the incidence of B cell tumor development.","volume-title":"J. Exp. Med.","year":"2008"},{"key":"2026012806314223000_R28","first-page":"630","article-title":"MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation.","volume-title":"Immunity","year":"2008"},{"key":"2026012806314223000_R29","first-page":"621","article-title":"MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase.","volume-title":"Immunity","year":"2008"},{"key":"2026012806314223000_R30","first-page":"2199","article-title":"miR-181b negatively regulates activation-induced cytidine deaminase in B cells.","volume-title":"J. Exp. Med.","year":"2008"},{"key":"2026012806314223000_R31","first-page":"2796","article-title":"DNA polymerase \u03b7 is a limiting factor for A:T mutations in Ig genes and contributes to antibody affinity maturation.","volume-title":"Eur. J. Immunol.","year":"2008"},{"key":"2026012806314223000_R32","first-page":"7696","article-title":"UV-B radiation induces epithelial tumors in mice lacking DNA polymerase \u03b7 and mesenchymal tumors in mice deficient for DNA polymerase \u03b9.","volume-title":"Mol. Cell. Biol.","year":"2006"},{"key":"2026012806314223000_R33","first-page":"87","article-title":"Increased susceptibility to UV-induced skin carcinogenesis in polymerase \u03b7-deficient mice.","volume-title":"Cancer Res.","year":"2006"},{"key":"2026012806314223000_R34","first-page":"265","article-title":"The absence of DNA polymerase \u03ba does not affect somatic hypermutation of the mouse immunoglobulin heavy chain gene.","volume-title":"Immunol. Lett.","year":"2003"},{"key":"2026012806314223000_R35","first-page":"2206","article-title":"Impaired translesion synthesis in xeroderma pigmentosum variant extracts.","volume-title":"Mol. Cell. Biol.","year":"1999"},{"key":"2026012806314223000_R36","first-page":"2055","article-title":"Xeroderma pigmentosum-variant patients from America, Europe, and Asia.","volume-title":"J. Invest. Dermatol.","year":"2008"},{"key":"2026012806314223000_R37","first-page":"1392","article-title":"Genetic analysis reveals an intrinsic property of the germinal center B cells to generate A:T mutations.","volume-title":"DNA Repair","year":"2008"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/10\/6353\/62687310\/9026.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/10\/6353\/62687310\/9026.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:34:59Z","timestamp":1769600099000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/182\/10\/6353\/8007109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,5]]},"references-count":37,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2009,5,15]]},"published-print":{"date-parts":[[2009,5,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0900177","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,5]]},"published":{"date-parts":[[2009,5]]}}}