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.
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Authors | Ahmad Faili, Said Aoufouchi, Sandra Weller, Françoise Vuillier, Anne Stary, Alain Sarasin, Claude-Agnès Reynaud, Jean-Claude Weill |
Journal | The Journal of experimental medicine
(J Exp Med)
Vol. 199
Issue 2
Pg. 265-70
(Jan 19 2004)
ISSN: 0022-1007 [Print] United States |
PMID | 14734526
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA Primers
- DNA
- DNA-Directed DNA Polymerase
- Rad30 protein
- AICDA (activation-induced cytidine deaminase)
- Cytosine Deaminase
- Cytidine Deaminase
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Topics |
- Adult
- B-Lymphocytes
(immunology)
- Base Sequence
- Cytidine Deaminase
- Cytosine Deaminase
(metabolism)
- DNA
(genetics)
- DNA Mutational Analysis
- DNA Primers
(genetics)
- DNA-Directed DNA Polymerase
(deficiency, genetics, metabolism)
- Female
- Humans
- Immunoglobulin Class Switching
- Immunologic Memory
- Introns
- Middle Aged
- Molecular Sequence Data
- Recombination, Genetic
- Somatic Hypermutation, Immunoglobulin
- Xeroderma Pigmentosum
(enzymology, genetics, immunology)
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