title: The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage.
abstract: 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.
authors: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Haiqing
authors: H
authors: Fu
authors: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Melvenia M
authors: MM
authors: Martin
authors: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Marie
authors: M
authors: Regairaz
authors: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Liang
authors: http://orcid.org/0000-0003-1663-7025
authors: L
authors: Huang
authors: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Yang
authors: Y
authors: You
authors: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Chi-Mei
authors: CM
authors: Lin
authors: InSilico Solutions, 11781 Lee Jackson Highway, Fairfax, Virginia 22033, USA.
authors: Michael
authors: M
authors: Ryan
authors: InSilico Solutions, 11781 Lee Jackson Highway, Fairfax, Virginia 22033, USA.
authors: RyangGuk
authors: R
authors: Kim
authors: Department of Environmental Health, National Institute of Public Health 2-3-6 Minami, Wako, Saitama 351-0197, Japan.
authors: Tsutomu
authors: T
authors: Shimura
authors: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Yves
authors: Y
authors: Pommier
authors: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Mirit I
authors: MI
authors: Aladjem
mesh_terms: D002453:Cell Cycle; D002470:Cell Survival / Q000235:genetics; D020552:Comet Assay; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D045325:HCT116 Cells; D006801:Humans
chemical_list: D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein; D004720:Endonucleases; C498772:MUS81 protein, human