Published online 13 January 2005
Article |
The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis
Department of Toxicogenetics, Leiden University Medical Center 2300 RA Leiden, The Netherlands 1 Division of Immunology, The Netherlands Cancer Institute 1066 CX Amsterdam, The Netherlands
*To whom correspondence should be addressed. Tel: +31 715271607; Fax: +31 715276173; Email: N.de_Wind{at}LUMC.nl
Received November 18, 2004. Revised December 22, 2004. Accepted December 22, 2004.
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. Rev1B/B mice are healthy, fertile and display normal somatic hypermutation. Rev1B/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 Rev1B/B cells, the opposite phenotype of UV-C-exposed cells from XP-V patients, lacking TLS polymerase 
. 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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Masuda, R. Ouchida, Y. Li, X. Gao, H. Mori, and J.-Y. Wang A Critical Role for REV1 in Regulating the Induction of C:G Transitions and A:T Mutations during Ig Gene Hypermutation J. Immunol., August 1, 2009; 183(3): 1846 - 1850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Jansen, A. Tsaalbi-Shtylik, G. Hendriks, H. Gali, A. Hendel, F. Johansson, K. Erixon, Z. Livneh, L. H. F. Mullenders, L. Haracska, et al. Separate Domains of Rev1 Mediate Two Modes of DNA Damage Bypass in Mammalian Cells Mol. Cell. Biol., June 1, 2009; 29(11): 3113 - 3123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Langerak, P. H.L Krijger, M. R Heideman, P. C.M van den Berk, and H. Jacobs Somatic hypermutation of immunoglobulin genes: lessons from proliferating cell nuclear antigenK164R mutant mice Phil Trans R Soc B, March 12, 2009; 364(1517): 621 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Waters, B. K. Minesinger, M. E. Wiltrout, S. D'Souza, R. V. Woodruff, and G. C. Walker Eukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance Microbiol. Mol. Biol. Rev., March 1, 2009; 73(1): 134 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Dumstorf, S. Mukhopadhyay, E. Krishnan, B. Haribabu, and W. G. McGregor REV1 Is Implicated in the Development of Carcinogen-Induced Lung Cancer Mol. Cancer Res., February 1, 2009; 7(2): 247 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kumar, W. S. Joo, G. Meinke, S. Moine, E. N. Naumova, and P. A. Bullock Evidence for a Structural Relationship between BRCT Domains and the Helicase Domains of the Replication Initiators Encoded by the Polyomaviridae and Papillomaviridae Families of DNA Tumor Viruses J. Virol., September 1, 2008; 82(17): 8849 - 8862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Guo, T.-S. Tang, M. Bienko, J. L. Parker, A. B. Bielen, E. Sonoda, S. Takeda, H. D. Ulrich, I. Dikic, and E. C. Friedberg Ubiquitin-Binding Motifs in REV1 Protein Are Required for Its Role in the Tolerance of DNA Damage Mol. Cell. Biol., December 1, 2006; 26(23): 8892 - 8900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ohkumo, Y. Kondo, M. Yokoi, T. Tsukamoto, A. Yamada, T. Sugimoto, R. Kanao, Y. Higashi, H. Kondoh, M. Tatematsu, et al. UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase {eta} and Mesenchymal Tumors in Mice Deficient for DNA Polymerase {iota} Mol. Cell. Biol., October 15, 2006; 26(20): 7696 - 7706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Masuda and K. Kamiya Role of Single-stranded DNA in Targeting REV1 to Primer Termini J. Biol. Chem., August 25, 2006; 281(34): 24314 - 24321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Waters and G. C. Walker The critical mutagenic translesion DNA polymerase Rev1 is highly expressed during G2/M phase rather than S phase PNAS, June 13, 2006; 103(24): 8971 - 8976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Jansen, P. Langerak, A. Tsaalbi-Shtylik, P. van den Berk, H. Jacobs, and N. de Wind Strand-biased defect in C/G transversions in hypermutating immunoglobulin genes in Rev1-deficient mice J. Exp. Med., February 21, 2006; 203(2): 319 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Martomo, W. W. Yang, R. P. Wersto, T. Ohkumo, Y. Kondo, M. Yokoi, C. Masutani, F. Hanaoka, and P. J. Gearhart Different mutation signatures in DNA polymerase {eta}- and MSH6-deficient mice suggest separate roles in antibody diversification PNAS, June 14, 2005; 102(24): 8656 - 8661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-L. Ross, L. J. Simpson, and J. E. Sale Vertebrate DNA damage tolerance requires the C-terminus but not BRCT or transferase domains of REV1 Nucleic Acids Res., March 1, 2005; 33(4): 1280 - 1289. [Abstract] [Full Text] [PDF]
|
|