E-type cyclins modulate telomere integrity in mammalian male meiosis
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  • 作者:Marcia Manterola ; Piotr Sicinski ; Debra J. Wolgemuth
  • 关键词:Meiosis ; E ; type cyclins ; Cyclin E1 ; Cyclin E2 ; Meiosis control ; Telomere ; Telomere integrity ; Shelterin complex ; TRF1 ; TRF2
  • 刊名:Chromosoma
  • 出版年:2016
  • 出版时间:June 2016
  • 年:2016
  • 卷:125
  • 期:2
  • 页码:253-264
  • 全文大小:761 KB
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  • 作者单位:Marcia Manterola (1)
    Piotr Sicinski (2) (3)
    Debra J. Wolgemuth (1) (4) (5)

    1. Department of Genetics & Development, Columbia University Medical Center, New York, NY, 10032, USA
    2. Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA
    3. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA
    4. Obstetrics & Gynecology, Columbia University Medical Center, New York, NY, 10032, USA
    5. Institute of Human Nutrition, Columbia University Medical Center, New York, NY, 10032, USA
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Life Sciences
    Cell Biology
    Developmental Biology
    Biochemistry
    Human Genetics
    Animal Genetics and Genomics
    Eukaryotic Microbiology
  • 出版者:Springer Berlin / Heidelberg
  • ISSN:1432-0886
文摘
We have shown that E-type cyclins are key regulators of mammalian male meiosis. Depletion of cyclin E2 reduced fertility in male mice due to meiotic defects, involving abnormal pairing and synapsis, unrepaired DNA, and loss of telomere structure. These defects were exacerbated by additional loss of cyclin E1, and complete absence of both E-type cyclins produces a meiotic catastrophe. Here, we investigated the involvement of E-type cyclins in maintaining telomere integrity in male meiosis. Spermatocytes lacking cyclin E2 and one E1 allele (E1+/-E2-/-) displayed a high rate of telomere abnormalities but can progress to pachytene and diplotene stages. We show that their telomeres exhibited an aberrant DNA damage repair response during pachynema and that the shelterin complex proteins TRF2 and RAP2 were significantly decreased in the proximal telomeres. Moreover, the insufficient level of these proteins correlated with an increase of γ-H2AX foci in the affected telomeres and resulted in telomere associations involving TRF1 and telomere detachment in later prophase-I stages. These results suggest that E-type cyclins are key modulators of telomere integrity during meiosis by, at least in part, maintaining the balance of shelterin complex proteins, and uncover a novel role of E-type cyclins in regulating chromosome structure during male meiosis.

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