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The Werner's Syndrome protein collaborates with REV1 to promote replication fork progression on damaged DNA
DNA damage tolerance pathways facilitate the bypass of DNA lesions encountered during replication. These pathways can be mechanistically divided into recombinational damage avoidance and translesion synthesis, in which the lesion is directly bypassed by specialised DNA polymerases. We have recently...
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Formato: | Texto |
Lenguaje: | English |
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Elsevier
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956782/ https://www.ncbi.nlm.nih.gov/pubmed/20691646 http://dx.doi.org/10.1016/j.dnarep.2010.07.006 |
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author | Phillips, Lara G. Sale, Julian E. |
author_facet | Phillips, Lara G. Sale, Julian E. |
author_sort | Phillips, Lara G. |
collection | PubMed |
description | DNA damage tolerance pathways facilitate the bypass of DNA lesions encountered during replication. These pathways can be mechanistically divided into recombinational damage avoidance and translesion synthesis, in which the lesion is directly bypassed by specialised DNA polymerases. We have recently shown distinct genetic dependencies for lesion bypass at and behind the replication fork in the avian cell line DT40, bypass at the fork requiring REV1 and bypass at post-replicative gaps requiring PCNA ubiquitination by RAD18. The WRN helicase/exonuclease, which is mutated in the progeroid and cancer predisposition disorder Werner's Syndrome, has previously been implicated in a RAD18-dependent DNA damage tolerance pathway. However, WRN has also been shown to be required to maintain normal replication fork progression on a damaged DNA template, a defect reminiscent of REV1-deficient cells. Here we use the avian cell line DT40 to demonstrate that WRN assists REV1-dependent translesion synthesis at the replication fork and that PCNA ubiquitination-dependent post-replicative lesion bypass provides an important backup mechanism for damage tolerance in the absence of WRN protein. |
format | Text |
id | pubmed-2956782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-29567822010-11-08 The Werner's Syndrome protein collaborates with REV1 to promote replication fork progression on damaged DNA Phillips, Lara G. Sale, Julian E. DNA Repair (Amst) Article DNA damage tolerance pathways facilitate the bypass of DNA lesions encountered during replication. These pathways can be mechanistically divided into recombinational damage avoidance and translesion synthesis, in which the lesion is directly bypassed by specialised DNA polymerases. We have recently shown distinct genetic dependencies for lesion bypass at and behind the replication fork in the avian cell line DT40, bypass at the fork requiring REV1 and bypass at post-replicative gaps requiring PCNA ubiquitination by RAD18. The WRN helicase/exonuclease, which is mutated in the progeroid and cancer predisposition disorder Werner's Syndrome, has previously been implicated in a RAD18-dependent DNA damage tolerance pathway. However, WRN has also been shown to be required to maintain normal replication fork progression on a damaged DNA template, a defect reminiscent of REV1-deficient cells. Here we use the avian cell line DT40 to demonstrate that WRN assists REV1-dependent translesion synthesis at the replication fork and that PCNA ubiquitination-dependent post-replicative lesion bypass provides an important backup mechanism for damage tolerance in the absence of WRN protein. Elsevier 2010-10-05 /pmc/articles/PMC2956782/ /pubmed/20691646 http://dx.doi.org/10.1016/j.dnarep.2010.07.006 Text en © 2010 Elsevier B.V. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Article Phillips, Lara G. Sale, Julian E. The Werner's Syndrome protein collaborates with REV1 to promote replication fork progression on damaged DNA |
title | The Werner's Syndrome protein collaborates with REV1 to promote replication fork progression on damaged DNA |
title_full | The Werner's Syndrome protein collaborates with REV1 to promote replication fork progression on damaged DNA |
title_fullStr | The Werner's Syndrome protein collaborates with REV1 to promote replication fork progression on damaged DNA |
title_full_unstemmed | The Werner's Syndrome protein collaborates with REV1 to promote replication fork progression on damaged DNA |
title_short | The Werner's Syndrome protein collaborates with REV1 to promote replication fork progression on damaged DNA |
title_sort | werner's syndrome protein collaborates with rev1 to promote replication fork progression on damaged dna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956782/ https://www.ncbi.nlm.nih.gov/pubmed/20691646 http://dx.doi.org/10.1016/j.dnarep.2010.07.006 |
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