Involvement of mammalian Mus81 in genome integrity and tumor suppression Journal Article
| Authors: | Mcpherson, J. P.; Lemmers, B.; Chahwan, R.; Pamidi, A.; Migon, E.; Matysiak-Zablocki, E.; Moynahan, M. E.; Essers, J.; Hanada, K.; Poonepalli, A.; Sanchez-Sweatman, O.; Khokha, R.; Kanaar, R.; Jasin, M.; Hande, M. P.; Hakem, R. |
| Article 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 γ-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. |
| Keywords: | controlled study; unclassified drug; dna-binding proteins; nonhuman; sensitivity analysis; neoplasms; t-lymphocytes; animal cell; mouse; meiosis; mammalia; animals; mice; dna damage; gene targeting; complex formation; genetic predisposition to disease; genes; biology; embryo; animal experiment; alleles; gene function; heterozygote; animalia; tumor suppressor gene; dna; genetic recombination; tumors; recombination, genetic; genomic instability; lymphoma; homozygote; stem cells; mitomycin c; gamma irradiation; sister chromatid exchange; genome; yeast; saccharomyces cerevisiae proteins; chromosome aberrations; endonuclease; mitomycin; mammals; dna cross linking; chromosomes; gene structure; tumor suppression; gene replication; cell dna; gamma rays; chromosome damage; genome integrity; endonucleases; mammalian genetics; male; female; priority journal; article; embryonic and fetal development; crosslinking; eme1 endonuclease; mus81 gene |
| Journal Title: | Science |
| Volume: | 304 |
| Issue: | 5678 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2004-06-18 |
| Start Page: | 1822 |
| End Page: | 1826 |
| Language: | English |
| DOI: | 10.1126/science.1094557 |
| PROVIDER: | scopus |
| PUBMED: | 15205536 |
| DOI/URL: | |
| Notes: | Science -- Cited By (since 1996):110 -- Export Date: 16 June 2014 -- CODEN: SCIEA -- Source: Scopus |
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