Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 3, Pages 592-597Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1618465114
Keywords
meiosis; telomere; Speedy A; Cdk2; germ cells
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Funding
- Jane and Dan Olssons Foundation
- LUA/ALF-medel Vastra Gotalandsregionen
- AFA Insurance
- Swedish Research Council
- Swedish Cancer Foundation, Sweden
- Biomedical Research Council of A*STAR (Agency for Science, Technology, and Research), Singapore
- Robert A. Welch Foundation Grant [E-0004]
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Telomere attachment to the nuclear envelope (NE) is a prerequisite for chromosomemovement duringmeiotic prophase I that is required for pairing of homologous chromosomes, synapsis, and homologous recombination. Here we show that Speedy A, a noncanonical activator of cyclin-dependent kinases (Cdks), is specifically localized to telomeres in prophase I male and female germ cells in mice, and plays an essential role in the telomere-NE attachment. Deletion of Spdya in mice disrupts telomere-NE attachment, and this impairs homologous pairing and synapsis and leads to zygotene arrest in male and female germ cells. In addition, we have identified a telomere localization domain on Speedy A covering the distal N terminus and the Cdk2-binding Ringo domain, and this domain is essential for the localization of Speedy A to telomeres. Furthermore, we found that the binding of Cdk2 to Speedy A is indispensable for Cdk2' s localization on telomeres, suggesting that Speedy A and Cdk2 might be the initial components that are recruited to the NE for forming the meiotic telomere complex. However, Speedy A-Cdk2-mediated telomere-NE attachment is independent of Cdk2 activation. Our results thus indicate that Speedy A and Cdk2 might mediate the initial telomere-NE attachment for the efficient assembly of the telomere complex that is essential for meiotic prophase I progression.
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