Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Fugger, Kasper, Mistrik, Martin, Danielsen, Jannie Rendtlew, Dinant, Christoffel, Falck, Jacob, Bartek, Jiri, Lukas, Jiri, Mailand, Niels
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
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
_version_ 1782171814357630976
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
work_keys_str_mv AT fuggerkasper humanfbh1helicasecontributestogenomemaintenanceviaproandantirecombinaseactivities
AT mistrikmartin humanfbh1helicasecontributestogenomemaintenanceviaproandantirecombinaseactivities
AT danielsenjannierendtlew humanfbh1helicasecontributestogenomemaintenanceviaproandantirecombinaseactivities
AT dinantchristoffel humanfbh1helicasecontributestogenomemaintenanceviaproandantirecombinaseactivities
AT falckjacob humanfbh1helicasecontributestogenomemaintenanceviaproandantirecombinaseactivities
AT bartekjiri humanfbh1helicasecontributestogenomemaintenanceviaproandantirecombinaseactivities
AT lukasjiri humanfbh1helicasecontributestogenomemaintenanceviaproandantirecombinaseactivities
AT mailandniels humanfbh1helicasecontributestogenomemaintenanceviaproandantirecombinaseactivities