title: The role of polymerase eta in somatic hypermutation determined by analysis of mutations in a patient with xeroderma pigmentosum variant.
abstract: To determine the possible role of polymerase eta (pol eta) in somatic hypermutation of B cells, a mutational analysis of 24 nonproductive rearrangements from a patient with xeroderma pigmentosum variant with a defect in pol eta was conducted. Although the mutational frequency of A and T bases decreased in WA (A/T, A) motifs, regardless of their RGYW (purine, G; pyrimidine, A/T) context, the overall mutational frequency of A or T bases was not affected. Moreover, the overall mutational frequency of the sequences examined was not decreased. There was an apparent increase in the number of insertions and deletions. The results are consistent with the conclusion that pol eta specifically targets WA motifs. However, its overall contribution to the somatic hypermutational process does not appear to be indispensable and in its absence other mechanisms maintain mutational activity.
authors.affiliation: Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
authors.forename: Sule
authors.initials: S
authors.lastname: Yavuz
authors.forename: Akif S
authors.initials: AS
authors.lastname: Yavuz
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Kraemer
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D020137:Base Pair Mismatch / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D017384:Sequence Deletion; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D014983:Xeroderma Pigmentosum / Q000201:enzymology* / Q000235:genetics*; D000099270:Y-Family DNA Polymerases
chemical_list: D004259:DNA-Directed DNA Polymerase; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases