title: Involvement of mammalian Mus81 in genome integrity and tumor suppression.
abstract: Mus81-Eme1 endonuclease has been implicated in the rescue of stalled replication forks and the resolution of meiotic recombination intermediates in yeast. We used gene targeting to study the physiological requirements of Mus81 in mammals. Mus81-/- mice are viable and fertile, which indicates that mammalian Mus81 is not essential for recombination processes associated with meiosis. Mus81-deficient mice and cells were hypersensitive to the DNA cross-linking agent mitomycin C but not to gamma-irradiation. Remarkably, both homozygous Mus81-/- and heterozygous Mus81+/- mice exhibited a similar susceptibility to spontaneous chromosomal damage and a profound and equivalent predisposition to lymphomas and other cancers. These studies demonstrate a critical role for the proper biallelic expression of the mammalian Mus81 in the maintenance of genomic integrity and tumor suppression.
authors.affiliation: Ontario Cancer Institute, 620 University Avenue, Suite 706, Toronto, Ontario, Canada M5G 2C1.
authors.forename: John Peter
authors.initials: JP
authors.lastname: McPherson
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Lemmers
authors.forename: Richard
authors.initials: R
authors.lastname: Chahwan
authors.forename: Ashwin
authors.initials: A
authors.lastname: Pamidi
authors.forename: Eva
authors.initials: E
authors.lastname: Migon
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Matysiak-Zablocki
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Moynahan
authors.forename: Jeroen
authors.initials: J
authors.lastname: Essers
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hanada
authors.forename: Anuradha
authors.initials: A
authors.lastname: Poonepalli
authors.forename: Otto
authors.initials: O
authors.lastname: Sanchez-Sweatman
authors.forename: Rama
authors.initials: R
authors.lastname: Khokha
authors.forename: Roland
authors.initials: R
authors.lastname: Kanaar
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
authors.forename: M Prakash
authors.initials: MP
authors.lastname: Hande
authors.forename: Razqallah
authors.initials: R
authors.lastname: Hakem
mesh_terms: D000483:Alleles; D000818:Animals; D002869:Chromosome Aberrations; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology; D005314:Embryonic and Fetal Development; D004720:Endonucleases; D005720:Gamma Rays; D018390:Gene Targeting; D020022:Genetic Predisposition to Disease; D016678:Genome; D042822:Genomic Instability; D006579:Heterozygote; D008223:Lymphoma / Q000209:etiology / Q000235:genetics / Q000473:pathology; D008540:Meiosis; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins; D012854:Sister Chromatid Exchange; D013234:Stem Cells; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D016685:Mitomycin; D004720:Endonucleases; C411624:MUS81 protein, S cerevisiae; C498773:Mus81 protein, mouse