title: DNA polymerase eta is involved in hypermutation occurring during immunoglobulin class switch recombination.
abstract: Base substitutions, deletions, and duplications are observed at the immunoglobulin locus in DNA sequences involved in class switch recombination (CSR). These mutations are dependent upon activation-induced cytidine deaminase (AID) and present all the characteristics of the ones observed during V gene somatic hypermutation, implying that they could be generated by the same mutational complex. It has been proposed, based on the V gene mutation pattern of patients with the cancer-prone xeroderma pigmentosum variant (XP-V) syndrome who are deficient in DNA polymerase eta (pol eta), that this enzyme could be responsible for a large part of the mutations occurring on A/T bases. Here we show, by analyzing switched memory B cells from two XP-V patients, that pol eta is also an A/T mutator during CSR, in both the switch region of tandem repeats as well as upstream of it, thus suggesting that the same error-prone translesional polymerases are involved, together with AID, in both processes.
authors.affiliation: INSERM U373, Faculté de Médecine Necker-Enfants Malades, Université Paris V, France.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Faili
authors.forename: Said
authors.initials: S
authors.lastname: Aoufouchi
authors.forename: Sandra
authors.initials: S
authors.lastname: Weller
authors.forename: Françoise
authors.initials: F
authors.lastname: Vuillier
authors.forename: Anne
authors.initials: A
authors.lastname: Stary
authors.forename: Alain
authors.initials: A
authors.lastname: Sarasin
authors.forename: Claude-Agnès
authors.initials: CA
authors.lastname: Reynaud
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Weill
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D017578:Immunoglobulin Class Switching; D007156:Immunologic Memory; D007438:Introns; D008875:Middle Aged; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin; D014983:Xeroderma Pigmentosum / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000099270:Y-Family DNA Polymerases
chemical_list: D003564:Cytidine Deaminase; D043525:Cytosine Deaminase; D004247:DNA; D017931:DNA Primers; D004259:DNA-Directed DNA Polymerase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases