Related Experiment Video
Updated: Mar 23, 2026
Spatiotemporal Analysis of Cytokinetic Events in Fission Yeast
Published on: February 20, 2017
Essential role of the Cdk2 activator RingoA in meiotic telomere tethering to the nuclear envelope
Petra Mikolcevic1, Michitaka Isoda1, Hiroki Shibuya2
1Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, Barcelona 08028, 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.
Insights
Mice lacking RingoA, a cyclin-independent activator, are sterile and show meiotic defects similar to Cdk2 knockout mice. RingoA is crucial for Cdk2 function at telomeres during meiosis.
Area of Science:
- Cell Biology
- Genetics
- Reproductive Biology
Background:
- Cyclin-dependent kinases (CDKs) are crucial regulators of the cell cycle.
- Cdk2 is essential for meiosis in mice, with Cdk2 knockout mice being sterile.
- RingoA is an atypical activator of CDKs, lacking homology to cyclins.
Purpose of the Study:
- To investigate the role of RingoA in meiosis and its relationship with Cdk2.
- To determine if RingoA's function in meiosis is dependent on cyclins.
Main Methods:
- Generation and analysis of RingoA knockout mice.
- Assessment of meiotic progression and chromosome pairing in RingoA-deficient spermatocytes.
- Examination of Cdk2 localization and telomere tethering in RingoA knockout mice.
Main Results:
- RingoA knockout mice exhibit sterility and meiotic defects mirroring Cdk2 knockout mice.
- Defects include non-homologous chromosome pairing, unrepaired double-strand breaks, and pachytene arrest.
- RingoA is essential for Cdk2 targeting to telomeres and proper telomere tethering via Sun1.
Conclusions:
- RingoA acts as a critical activator of Cdk2 at meiotic telomeres.
- This study provides genetic evidence for a cyclin-independent physiological function of mammalian Cdk2.
Related Concept Videos
02:15The Contractile Ring
A small GTPase, RhoA, controls the function and assembly of the contractile ring. RhoA belongs to the Ras superfamily of proteins. The activation of formins by RhoA promotes...
02:15The Contractile Ring
02:41Telomeres and Telomerase
02:41Telomeres and Telomerase
01:29Replication in Eukaryotes
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
02:31Replication in Eukaryotes