DNA repair protein REV1
somatic hypermutation of immunoglobulin genes
The catalytic activity of REV1 is employed during immunoglobulin gene diversification in DT40.
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 REV1 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.