Speedy A-Cdk2 binding mediates initial telomere-nuclear envelope attachment during meiotic prophase i independent of Cdk2 activation

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Zhaowei Tu
  • Mustafa Bilal Bayazit
  • Hongbin Liu
  • Jingjing Zhang
  • Kiran Busayavalasa
  • Sanjiv Risal
  • Jingchen Shao
  • Ande Satyanarayana
  • Vincenzo Coppola
  • Lino Tessarollo
  • Meenakshi Singh
  • Chunwei Zheng
  • Chunsheng Han
  • Zijiang Chen
  • Philipp Kaldis
  • Jan Åke Gustafsson
  • Kui Liu
External organisations
  • University of Gothenburg
  • Shandong University
  • National Cancer Institute at Frederick
  • Georgia Regents University
  • Ohio State University
  • Institute of Zoology Chinese Academy of Sciences
  • A*Star Institute of Molecular and Cell Biology (IMCB)
  • National University of Singapore
  • University of Houston
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • Cdk2, Germ cells, Meiosis, Speedy A, Telomere
Original languageEnglish
Pages (from-to)592-597
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number3
Publication statusPublished - 2017 Jan 17
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes