Journal
MOLECULAR IMMUNOLOGY
Volume 43, Issue 10, Pages 1587-1594Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2005.09.017
Keywords
REV1; translesion synthesis; immunoglobulin gene; somatic hypermutation; DNA damage tolerance
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Funding
- Medical Research Council [MC_U105178808] Funding Source: Medline
- MRC [MC_U105178808] Funding Source: UKRI
- Medical Research Council [MC_U105178808] Funding Source: researchfish
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REV1 plays a key role in vertebrate translesion synthesis. Although its deoxycytidyl transferase activity is dispensable for tolerance of DNA damage caused by a number of mutagens, its extreme C terminus, which interacts with other translesion polymerases and PCNA. is essential. By examining immunoglobulin diversification in the genetically tractable chicken cell line DT40 we show that the generation of non-templated point mutations from C/G to G/C does require the catalytic activity of REV1. This provides the first clear evidence that the catalytic activity of REV I is utilised in vivo in higher eukaryotes and is involved in immunoglobulin diversification. Although rev1 DT40 cells incorporate few point mutations, a mutant lacking the C terminus of REV1 exhibits a similar level to that seen in wild-type cells. Thus, the polymerase selection or stabilisation role of REV1 does not appear to play a major role in the bypass of AID-dependent abasic sites. (c) 2005 Elsevier Ltd. All rights reserved.
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