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The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis
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...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC546167/ https://www.ncbi.nlm.nih.gov/pubmed/15653636 http://dx.doi.org/10.1093/nar/gki189 |
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author | Jansen, Jacob G. Tsaalbi-Shtylik, Anastasia Langerak, Petra Calléja, Fabienne Meijers, Caro M. Jacobs, Heinz de Wind, Niels |
author_facet | Jansen, Jacob G. Tsaalbi-Shtylik, Anastasia Langerak, Petra Calléja, Fabienne Meijers, Caro M. Jacobs, Heinz de Wind, Niels |
author_sort | Jansen, Jacob G. |
collection | PubMed |
description | 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 η. 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. |
format | Text |
id | pubmed-546167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-5461672005-02-07 The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis Jansen, Jacob G. Tsaalbi-Shtylik, Anastasia Langerak, Petra Calléja, Fabienne Meijers, Caro M. Jacobs, Heinz de Wind, Niels Nucleic Acids Res Article 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 η. 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. Oxford University Press 2005 2005-01-13 /pmc/articles/PMC546167/ /pubmed/15653636 http://dx.doi.org/10.1093/nar/gki189 Text en © 2005, the authors Nucleic Acids Research, Vol. 33 No. 1 © Oxford University Press 2005; all rights reserved |
spellingShingle | Article Jansen, Jacob G. Tsaalbi-Shtylik, Anastasia Langerak, Petra Calléja, Fabienne Meijers, Caro M. Jacobs, Heinz de Wind, Niels The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis |
title | The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis |
title_full | The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis |
title_fullStr | The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis |
title_full_unstemmed | The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis |
title_short | The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis |
title_sort | brct domain of mammalian rev1 is involved in regulating dna translesion synthesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC546167/ https://www.ncbi.nlm.nih.gov/pubmed/15653636 http://dx.doi.org/10.1093/nar/gki189 |
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