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The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage

The Mus81 endonuclease resolves recombination intermediates and mediates cellular responses to exogenous replicative stress. Here, we show that Mus81 also regulates the rate of DNA replication during normal growth by promoting replication fork progression while reducing the frequency of replication...

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Autores principales: Fu, Haiqing, Martin, Melvenia M., Regairaz, Marie, Huang, Liang, You, Yang, Lin, Chi-Mei, Ryan, Michael, Kim, RyangGuk, Shimura, Tsutomu, Pommier, Yves, Aladjem, Mirit I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400873/
https://www.ncbi.nlm.nih.gov/pubmed/25879486
http://dx.doi.org/10.1038/ncomms7746
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author Fu, Haiqing
Martin, Melvenia M.
Regairaz, Marie
Huang, Liang
You, Yang
Lin, Chi-Mei
Ryan, Michael
Kim, RyangGuk
Shimura, Tsutomu
Pommier, Yves
Aladjem, Mirit I.
author_facet Fu, Haiqing
Martin, Melvenia M.
Regairaz, Marie
Huang, Liang
You, Yang
Lin, Chi-Mei
Ryan, Michael
Kim, RyangGuk
Shimura, Tsutomu
Pommier, Yves
Aladjem, Mirit I.
author_sort Fu, Haiqing
collection PubMed
description The Mus81 endonuclease resolves recombination intermediates and mediates cellular responses to exogenous replicative stress. Here, we show that Mus81 also regulates the rate of DNA replication during normal growth by promoting replication fork progression while reducing the frequency of replication initiation events. In the absence of Mus81 endonuclease activity, DNA synthesis is slowed and replication initiation events are more frequent. In addition, Mus81 deficient cells fail to recover from exposure to low doses of replication inhibitors and cell viability is dependent on the XPF endonuclease. Despite an increase in replication initiation frequency, cells lacking Mus81 use the same pool of replication origins as Mus81-expressing cells. Therefore, decelerated DNA replication in Mus81 deficient cells does not initiate from cryptic or latent origins not used during normal growth. These results indicate that Mus81 plays a key role in determining the rate of DNA replication without activating a novel group of replication origins.
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spelling pubmed-44008732015-10-16 The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage Fu, Haiqing Martin, Melvenia M. Regairaz, Marie Huang, Liang You, Yang Lin, Chi-Mei Ryan, Michael Kim, RyangGuk Shimura, Tsutomu Pommier, Yves Aladjem, Mirit I. Nat Commun Article The Mus81 endonuclease resolves recombination intermediates and mediates cellular responses to exogenous replicative stress. Here, we show that Mus81 also regulates the rate of DNA replication during normal growth by promoting replication fork progression while reducing the frequency of replication initiation events. In the absence of Mus81 endonuclease activity, DNA synthesis is slowed and replication initiation events are more frequent. In addition, Mus81 deficient cells fail to recover from exposure to low doses of replication inhibitors and cell viability is dependent on the XPF endonuclease. Despite an increase in replication initiation frequency, cells lacking Mus81 use the same pool of replication origins as Mus81-expressing cells. Therefore, decelerated DNA replication in Mus81 deficient cells does not initiate from cryptic or latent origins not used during normal growth. These results indicate that Mus81 plays a key role in determining the rate of DNA replication without activating a novel group of replication origins. 2015-04-16 /pmc/articles/PMC4400873/ /pubmed/25879486 http://dx.doi.org/10.1038/ncomms7746 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Fu, Haiqing
Martin, Melvenia M.
Regairaz, Marie
Huang, Liang
You, Yang
Lin, Chi-Mei
Ryan, Michael
Kim, RyangGuk
Shimura, Tsutomu
Pommier, Yves
Aladjem, Mirit I.
The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage
title The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage
title_full The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage
title_fullStr The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage
title_full_unstemmed The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage
title_short The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage
title_sort dna repair endonuclease mus81 facilitates fast dna replication in the absence of exogenous damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400873/
https://www.ncbi.nlm.nih.gov/pubmed/25879486
http://dx.doi.org/10.1038/ncomms7746
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