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Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities
Homologous recombination (HR) is essential for faithful repair of DNA lesions yet must be kept in check, as unrestrained HR may compromise genome integrity and lead to premature aging or cancer. To limit unscheduled HR, cells possess DNA helicases capable of preventing excessive recombination. In th...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2742184/ https://www.ncbi.nlm.nih.gov/pubmed/19736316 http://dx.doi.org/10.1083/jcb.200812138 |
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author | Fugger, Kasper Mistrik, Martin Danielsen, Jannie Rendtlew Dinant, Christoffel Falck, Jacob Bartek, Jiri Lukas, Jiri Mailand, Niels |
author_facet | Fugger, Kasper Mistrik, Martin Danielsen, Jannie Rendtlew Dinant, Christoffel Falck, Jacob Bartek, Jiri Lukas, Jiri Mailand, Niels |
author_sort | Fugger, Kasper |
collection | PubMed |
description | Homologous recombination (HR) is essential for faithful repair of DNA lesions yet must be kept in check, as unrestrained HR may compromise genome integrity and lead to premature aging or cancer. To limit unscheduled HR, cells possess DNA helicases capable of preventing excessive recombination. In this study, we show that the human Fbh1 (hFbh1) helicase accumulates at sites of DNA damage or replication stress in a manner dependent fully on its helicase activity and partially on its conserved F box. hFbh1 interacted with single-stranded DNA (ssDNA), the formation of which was required for hFbh1 recruitment to DNA lesions. Conversely, depletion of endogenous Fbh1 or ectopic expression of helicase-deficient hFbh1 attenuated ssDNA production after replication block. Although elevated levels of hFbh1 impaired Rad51 recruitment to ssDNA and suppressed HR, its small interfering RNA–mediated depletion increased the levels of chromatin-associated Rad51 and caused unscheduled sister chromatid exchange. Thus, by possessing both pro- and anti-recombinogenic potential, hFbh1 may cooperate with other DNA helicases in tightly controlling cellular HR activity. |
format | Text |
id | pubmed-2742184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27421842010-03-07 Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities Fugger, Kasper Mistrik, Martin Danielsen, Jannie Rendtlew Dinant, Christoffel Falck, Jacob Bartek, Jiri Lukas, Jiri Mailand, Niels J Cell Biol Research Articles Homologous recombination (HR) is essential for faithful repair of DNA lesions yet must be kept in check, as unrestrained HR may compromise genome integrity and lead to premature aging or cancer. To limit unscheduled HR, cells possess DNA helicases capable of preventing excessive recombination. In this study, we show that the human Fbh1 (hFbh1) helicase accumulates at sites of DNA damage or replication stress in a manner dependent fully on its helicase activity and partially on its conserved F box. hFbh1 interacted with single-stranded DNA (ssDNA), the formation of which was required for hFbh1 recruitment to DNA lesions. Conversely, depletion of endogenous Fbh1 or ectopic expression of helicase-deficient hFbh1 attenuated ssDNA production after replication block. Although elevated levels of hFbh1 impaired Rad51 recruitment to ssDNA and suppressed HR, its small interfering RNA–mediated depletion increased the levels of chromatin-associated Rad51 and caused unscheduled sister chromatid exchange. Thus, by possessing both pro- and anti-recombinogenic potential, hFbh1 may cooperate with other DNA helicases in tightly controlling cellular HR activity. The Rockefeller University Press 2009-09-07 /pmc/articles/PMC2742184/ /pubmed/19736316 http://dx.doi.org/10.1083/jcb.200812138 Text en © 2009 Fugger et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Fugger, Kasper Mistrik, Martin Danielsen, Jannie Rendtlew Dinant, Christoffel Falck, Jacob Bartek, Jiri Lukas, Jiri Mailand, Niels Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities |
title | Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities |
title_full | Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities |
title_fullStr | Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities |
title_full_unstemmed | Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities |
title_short | Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities |
title_sort | human fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2742184/ https://www.ncbi.nlm.nih.gov/pubmed/19736316 http://dx.doi.org/10.1083/jcb.200812138 |
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