| First Author | Jansen JG | Year | 2005 |
| Journal | Nucleic Acids Res | Volume | 33 |
| Issue | 1 | Pages | 356-65 |
| PubMed ID | 15653636 | Mgi Jnum | J:150258 |
| Mgi Id | MGI:3850223 | Doi | 10.1093/nar/gki189 |
| Citation | Jansen JG, et al. (2005) The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis. Nucleic Acids Res 33(1):356-65 |
| abstractText | Rev1 is a deoxycytidyl transferase associated with DNA translesion synthesis (TLS). In addition to its catalytic domain, Rev1 possesses a so-called BRCA1 C-terminal (BRCT) domain. Here, we describe cells and mice containing a targeted deletion of this domain. Rev1(B/B) mice are healthy, fertile and display normal somatic hypermutation. Rev1(B/B) cells display an elevated spontaneous frequency of intragenic deletions at Hprt. In addition, these cells were sensitized to exogenous DNA damages. Ultraviolet-C (UV-C) light induced a delayed progression through late S and G2 phases of the cell cycle and many chromatid aberrations, specifically in a subset of mutant cells, but not enhanced sister chromatid exchanges (SCE). UV-C-induced mutagenesis was reduced and mutations at thymidine-thymidine dimers were absent in Rev1(B/B) cells, the opposite phenotype of UV-C-exposed cells from XP-V patients, lacking TLS polymerase eta. This suggests that the enhanced UV-induced mutagenesis in XP-V patients may depend on error-prone Rev1-dependent TLS. Together, these data indicate a regulatory role of the Rev1 BRCT domain in TLS of a limited spectrum of endogenous and exogenous nucleotide damages during a defined phase of the cell cycle. |
