B-LYMPHOCYTES OF XERODERMA-PIGMENTOSUM OR COCKAYNE-SYNDROME PATIENTS WITH INHERITED DEFECTS IN NUCLEOTIDE EXCISION-REPAIR ARE FULLY CAPABLEOF SOMATIC HYPERMUTATION OF IMMUNOGLOBULIN GENES

Recent experiments have strongly suggested that the process of somatic mutation is linked to transcription initiation. It was postulated tha t a mutator factor loads onto the RNA polymerase and, during elongatio n, causes transcriptional arrest that activates DNA repair, thus occas ionally causing errors in the DNA sequence. We report the analysis of the role of one of the known DNA repair systems, nucleotide excision r epair (NER), in somatic mutation. Epstein-Barr-virus-transformed B cel ls from patients with defects in NER (XP-B, XP-D, XP-V, and CS-A) were studied. Their heavy and light chain genes show a high frequency of p oint mutations in the variable (V), but not in the constant (C) region s. This suggests that these B cells can undergo somatic hypermutation despite significant defects in NER. Thus, it is doubtful that NER is a n essential part of the mechanism of somatic hypermutation of Ig genes . As an aside, NER seems also not involved in Ig gene switch recombina tion.