2. Academic Validation
  3. Speedy A-Cdk2 binding mediates initial telomere-nuclear envelope attachment during meiotic prophase I independent of Cdk2 activation

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

  • Proc Natl Acad Sci U S A. 2017 Jan 17;114(3):592-597. doi: 10.1073/pnas.1618465114.
Zhaowei Tu 1,  Mustafa Bilal Bayazit 1,  Hongbin Liu 2,  Jingjing Zhang 1,  Kiran Busayavalasa 1,  Sanjiv Risal 1,  Jingchen Shao 1,  Ande Satyanarayana 3,  Vincenzo Coppola 3,  Lino Tessarollo 3,  Meenakshi Singh 1,  Chunwei Zheng 4,  Chunsheng Han 4,  Zijiang Chen 2,  Philipp Kaldis 5 6,  Jan-Åke Gustafsson 7,  Kui Liu 8 2
Affiliations

Affiliations

  • 1 Department of Chemistry and Molecular Biology, University of Gothenburg, SE-40530 Gothenburg, Sweden.
  • 2 The Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan 250001, China.
  • 3 Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201.
  • 4 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  • 5 Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore 138673, Republic of Singapore; kaldis@imcb.a-star.edu.sg jgustafs@central.uh.edu kui.liu@gu.se.
  • 6 Department of Biochemistry, National University of Singapore, Singapore 117599, Republic of Singapore.
  • 7 Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204 kaldis@imcb.a-star.edu.sg jgustafs@central.uh.edu kui.liu@gu.se.
  • 8 Department of Chemistry and Molecular Biology, University of Gothenburg, SE-40530 Gothenburg, Sweden; kaldis@imcb.a-star.edu.sg jgustafs@central.uh.edu kui.liu@gu.se.
PMID: 28031483 DOI: 10.1073/pnas.1618465114
Abstract

Telomere attachment to the nuclear envelope (NE) is a prerequisite for chromosome movement during meiotic 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.

Keywords

Cdk2; Speedy A; germ cells; meiosis; telomere.

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