title: Gen1 and Eme1 Play Redundant Roles in DNA Repair and Meiotic Recombination in Mice.
abstract: Resolution of the Holliday junction (HJ) is essential for homologous recombination and DNA repair. In Saccharomyces cerevisiae, HJ resolvase Yen1 and the Mus81-Mms4 complex are redundant in DNA damage repair. In cultured mammalian cells, such redundancy also exists between Yen1 ortholog GEN1 and the Mus81-Mms1 ortholog MUS81-EME1. In this report, we further tested if GEN1 and EME1 redundantly affect HJ-related physiological processes in mice. We found that combined homozygous mutations of Gen1 and Eme1 led to synthetic lethality during early embryonic stages. Homozygous Gen1 mutations did not cause DNA repair deficiency in mouse embryonic fibroblast (MEF) cells, but made heterozygous Eme1 mutant MEFs more sensitive to various DNA-damaging reagents. Gen1 mutations also reduced the meiotic recombination efficiency in Eme1 mutant mice. These results suggest that Gen1 and Eme1 play redundant roles in DNA repair and meiotic recombination in vivo.
authors.affiliation: 1 Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children's Hospital of Fudan University , Shanghai, China .|2 Department of Nephrology, Wuhan Medical and Healthcare Center for Women and Children , Wuhan, China .
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wang
authors.affiliation: 3 State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University , Shanghai, China .|4 Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland.
authors.forename: Herui
authors.initials: H
authors.lastname: Wang
authors.affiliation: 3 State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University , Shanghai, China .
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.affiliation: 1 Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children's Hospital of Fudan University , Shanghai, China .
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1 Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children's Hospital of Fudan University , Shanghai, China .
authors.forename: Yinv
authors.initials: Y
authors.lastname: Gong
authors.affiliation: 3 State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University , Shanghai, China .|5 Department of Molecular, Cellular, and Developmental Biology, University of Colorado , Boulder, Colorado.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 1 Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children's Hospital of Fudan University , Shanghai, China .
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: 1 Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children's Hospital of Fudan University , Shanghai, China .|3 State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University , Shanghai, China .
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D045566:DNA, Cruciform; D004622:Embryo, Mammalian / Q000166:cytology; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D045565:Holliday Junction Resolvases / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis; D051379:Mice; D016254:Mutagenesis, Insertional; D011995:Recombination, Genetic
chemical_list: D045566:DNA, Cruciform; C000599653:GEN1 protein, mouse; C480534:Eme1 protein, mouse; D004706:Endodeoxyribonucleases; D045565:Holliday Junction Resolvases
keywords: DNA repair; Eme1; Gen1; meiotic recombination