Abstract
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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Acknowledgments
The authors would like to thank Dr. Titia de Lange for kindly providing the anti-TRF1 and RAP1 antibodies and Dr. Manfred Alsheimer for providing the anti-LAP2 antibody. This work was supported in part by grants from the NIH, R01 HD034915 (DJW) and R01 CA083688 (PS), and the Lalor Foundation (MM).
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This article is part of a Special Issue on “Recent advances in meiotic chromosome structure, recombination and segregation” edited by Marco Barchi, Paula Cohen and Scott Keeney.
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Manterola, M., Sicinski, P. & Wolgemuth, D.J. E-type cyclins modulate telomere integrity in mammalian male meiosis. Chromosoma 125, 253–264 (2016). https://doi.org/10.1007/s00412-015-0564-3
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DOI: https://doi.org/10.1007/s00412-015-0564-3