Abstract |
After gene rearrangement, immunoglobulin V genes are further diversified by either somatic hypermutation or gene conversion. Hypermutation (in man and mouse) occurs by the fixation of individual, non-templated nucleotide substitutions. Gene conversion (in chicken) is templated by a set of upstream V pseudogenes. Here we show that if the RAD51 paralogues XRCC2, XRCC3 or RAD51B are ablated the pattern of diversification of the immunoglobulin V gene in the chicken DT40 B-cell lymphoma line exhibits a marked shift from one of gene conversion to one of somatic hypermutation. Non-templated, single- nucleotide substitutions are incorporated at high frequency specifically into the V domain, largely at G/C and with a marked hotspot preference. These mutant DT40 cell lines provide a tractable model for the genetic dissection of immunoglobulin hypermutation and the results support the idea that gene conversion and somatic hypermutation constitute distinct pathways for processing a common lesion in the immunoglobulin V gene. The marked induction of somatic hypermutation that is achieved by ablating the RAD51 paralogues is probably a consequence of modifying the recombination-mediated repair of such initiating lesions.
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Authors | J E Sale, D M Calandrini, M Takata, S Takeda, M S Neuberger |
Journal | Nature
(Nature)
Vol. 412
Issue 6850
Pg. 921-6
(Aug 30 2001)
ISSN: 0028-0836 [Print] England |
PMID | 11528482
(Publication Type: Journal Article)
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Chemical References |
- DNA-Binding Proteins
- Immunoglobulin Variable Region
- X-ray repair cross complementing protein 3
- Xrcc2 protein, mouse
- DNA
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Topics |
- Animals
- B-Lymphocytes
(immunology)
- Base Sequence
- Cell Line
- Chickens
- Clone Cells
- DNA
- DNA Damage
- DNA Repair
- DNA-Binding Proteins
(genetics, physiology)
- Gene Conversion
- Immunoglobulin Variable Region
(genetics)
- Molecular Sequence Data
- Mutation
- Tumor Cells, Cultured
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