title: Mammalian E-type cyclins control chromosome pairing, telomere stability and CDK2 localization in male meiosis.
abstract: Loss of function of cyclin E1 or E2, important regulators of the mitotic cell cycle, yields viable mice, but E2-deficient males display reduced fertility. To elucidate the role of E-type cyclins during spermatogenesis, we characterized their expression patterns and produced additional deletions of Ccne1 and Ccne2 alleles in the germline, revealing unexpected meiotic functions. While Ccne2 mRNA and protein are abundantly expressed in spermatocytes, Ccne1 mRNA is present but its protein is detected only at low levels. However, abundant levels of cyclin E1 protein are detected in spermatocytes deficient in cyclin E2 protein. Additional depletion of E-type cyclins in the germline resulted in increasingly enhanced spermatogenic abnormalities and corresponding decreased fertility and loss of germ cells by apoptosis. Profound meiotic defects were observed in spermatocytes, including abnormal pairing and synapsis of homologous chromosomes, heterologous chromosome associations, unrepaired double-strand DNA breaks, disruptions in telomeric structure and defects in cyclin-dependent-kinase 2 localization. These results highlight a new role for E-type cyclins as important regulators of male meiosis.
authors.affiliation: Departments of Genetics & Development, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Martinerie
authors.affiliation: Departments of Genetics & Development, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Marcia
authors.initials: M
authors.lastname: Manterola
authors.affiliation: Departments of Genetics & Development, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Sanny S W
authors.initials: SS
authors.lastname: Chung
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Panigrahi
authors.affiliation: Departments of Genetics & Development, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Weisbach
authors.affiliation: Departments of Genetics & Development, Columbia University Medical Center, New York, New York, United States of America ; Center for Radiological Research, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Ana
authors.initials: A
authors.lastname: Vasileva
authors.affiliation: Department of Genetics, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Genetics, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Sicinski
authors.affiliation: Departments of Genetics & Development, Columbia University Medical Center, New York, New York, United States of America ; Obstetrics & Gynecology, Columbia University Medical Center, New York, New York, United States of America ; Institute of Human Nutrition, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Wolgemuth
mesh_terms: D000818:Animals; D023902:Chromosome Pairing / Q000235:genetics; D019927:Cyclin E / Q000096:biosynthesis / Q000235:genetics*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics* / Q000378:metabolism; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D008540:Meiosis; D051379:Mice; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D013090:Spermatocytes / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics; D016615:Telomere / Q000235:genetics; D013737:Testis / Q000378:metabolism
chemical_list: C503689:Ccne2 protein, mouse; D019927:Cyclin E; D016213:Cyclins; D015513:Oncogene Proteins; C568314:cyclin E1, mouse; D051357:Cyclin-Dependent Kinase 2