The catalytic activity of REV1 is employed during immunoglobulin gene diversification in DT40
- PMID: 16263170
- DOI: 10.1016/j.molimm.2005.09.017
The catalytic activity of REV1 is employed during immunoglobulin gene diversification in DT40
Abstract
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.
Similar articles
-
Vertebrate DNA damage tolerance requires the C-terminus but not BRCT or transferase domains of REV1.Nucleic Acids Res. 2005 Mar 1;33(4):1280-9. doi: 10.1093/nar/gki279. Print 2005. Nucleic Acids Res. 2005. PMID: 15741181 Free PMC article.
-
Strand-biased defect in C/G transversions in hypermutating immunoglobulin genes in Rev1-deficient mice.J Exp Med. 2006 Feb 20;203(2):319-23. doi: 10.1084/jem.20052227. Epub 2006 Feb 13. J Exp Med. 2006. PMID: 16476771 Free PMC article.
-
Rev1 is essential for DNA damage tolerance and non-templated immunoglobulin gene mutation in a vertebrate cell line.EMBO J. 2003 Apr 1;22(7):1654-64. doi: 10.1093/emboj/cdg161. EMBO J. 2003. PMID: 12660171 Free PMC article.
-
Immunoglobulin diversification in DT40: a model for vertebrate DNA damage tolerance.DNA Repair (Amst). 2004 Jul 2;3(7):693-702. doi: 10.1016/j.dnarep.2004.03.042. DNA Repair (Amst). 2004. PMID: 15177178 Review.
-
Activation-induced cytidine deaminase-mediated hypermutation in the DT40 cell line.Philos Trans R Soc Lond B Biol Sci. 2009 Mar 12;364(1517):639-44. doi: 10.1098/rstb.2008.0202. Philos Trans R Soc Lond B Biol Sci. 2009. PMID: 19008193 Free PMC article. Review.
Cited by
-
The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ.Nucleic Acids Res. 2015 Feb 18;43(3):1671-83. doi: 10.1093/nar/gkv023. Epub 2015 Jan 27. Nucleic Acids Res. 2015. PMID: 25628356 Free PMC article.
-
Creation and resolution of non-B-DNA structural impediments during replication.Crit Rev Biochem Mol Biol. 2022 Aug;57(4):412-442. doi: 10.1080/10409238.2022.2121803. Epub 2022 Sep 28. Crit Rev Biochem Mol Biol. 2022. PMID: 36170051 Free PMC article.
-
Molecular mechanisms of avian immunoglobulin gene diversification and prospect for industrial applications.Front Immunol. 2024 Sep 13;15:1453833. doi: 10.3389/fimmu.2024.1453833. eCollection 2024. Front Immunol. 2024. PMID: 39346918 Free PMC article. Review.
-
What a difference a decade makes: insights into translesion DNA synthesis.Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15591-8. doi: 10.1073/pnas.0704219104. Epub 2007 Sep 26. Proc Natl Acad Sci U S A. 2007. PMID: 17898175 Free PMC article.
-
Mechanisms of DNA Damage Tolerance: Post-Translational Regulation of PCNA.Genes (Basel). 2018 Dec 24;10(1):10. doi: 10.3390/genes10010010. Genes (Basel). 2018. PMID: 30586904 Free PMC article. Review.
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous