title: Involvement of Rad18 in somatic hypermutation.
abstract: Somatic hypermutation of Ig genes is initiated by transcription-coupled cytidine deamination in Ig loci. Error-prone processing of the resultant DNA lesions is thought to cause extensive mutagenesis, but it is presently an enigma how and why error-prone rather than error-free repair pathways are recruited. During DNA replication, recruitment of error-prone translesion polymerases may be mediated by Rad6/Rad18-mediated ubiquitination of proliferating cell nuclear antigen, a major switchboard controlling the fidelity of DNA lesion bypass in eukaryotes. By inactivation of Rad18 in the DT40 B cell line, we show that the Rad6 pathway is involved in somatic hypermutation in these cells. Our findings imply that targeted recruitment of mutagenic polymerases by the Rad6 pathway contributes to the complex process of somatic hypermutation and provide a framework for more detailed mechanistic studies of the mutagenesis phase of secondary Ig diversification.
authors.affiliation: Institute of Clinical Molecular Biology and Tumor Genetics, GSF-Research Center for Environment and Health, Marchioninistrasse 25, 81377 Munich, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bachl
authors.forename: Isin
authors.initials: I
authors.lastname: Ertongur
authors.forename: Berit
authors.initials: B
authors.lastname: Jungnickel
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D003562:Cytidine / Q000737:chemistry; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000502:physiology*; D008957:Models, Genetic; D009154:Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000502:physiology; D014158:Transcription, Genetic; D019076:Transgenes; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000502:physiology; D044767:Ubiquitin-Protein Ligases
chemical_list: D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; C485954:RAD18 protein, human; D025801:Ubiquitin; D003562:Cytidine; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases