Format

Send to

Choose Destination
Nat Commun. 2016 Mar 30;7:11084. doi: 10.1038/ncomms11084.

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

Author information

1
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
2
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
3
Unidad de Biología Celular, Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid 28049, Spain.
4
Department of Molecular and Cell Biology, Henry Wellcome Building, University of Leicester, Leicester LE1 9HN, UK.
5
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain.

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.

PMID:
27025256
PMCID:
PMC4820962
DOI:
10.1038/ncomms11084
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center