Essential role of the Cdk2 activator RingoA in meiotic telomere tethering to the nuclear envelope

Petra Mikolcevic, Michitaka Isoda, Hiroki Shibuya, Ivan del Barco Barrantes, Ana Igea, José A. Suja, Sue Shackleton, Yoshinori Watanabe and Angel R. Nebreda ()
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Petra Mikolcevic: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology
Michitaka Isoda: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology
Hiroki Shibuya: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo
Ivan del Barco Barrantes: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology
Ana Igea: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology
José A. Suja: Unidad de Biología Celular, Facultad de Ciencias, Universidad Autónoma de Madrid
Sue Shackleton: Henry Wellcome Building, University of Leicester
Yoshinori Watanabe: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo
Angel R. Nebreda: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Cyclin-dependent kinases (CDKs) play key roles in cell cycle regulation. Genetic analysis in mice has revealed an essential role for Cdk2 in meiosis, which renders Cdk2 knockout (KO) mice sterile. Here we show that mice deficient in RingoA, an atypical activator of Cdk1 and Cdk2 that has no amino acid sequence homology to cyclins, are sterile and display meiotic defects virtually identical to those observed in Cdk2 KO mice including non-homologous chromosome pairing, unrepaired double-strand breaks, undetectable sex-body and pachytene arrest. Interestingly, RingoA is required for Cdk2 targeting to telomeres and RingoA KO spermatocytes display severely affected telomere tethering as well as impaired distribution of Sun1, a protein essential for the attachment of telomeres to the nuclear envelope. Our results identify RingoA as an important activator of Cdk2 at meiotic telomeres, and provide genetic evidence for a physiological function of mammalian Cdk2 that is not dependent on cyclins.

Date: 2016
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DOI: 10.1038/ncomms11084

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