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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 114; no. 3; pp. 592 - 597
• Main Authors: Tu, Zhaowei, Bayazit, Mustafa Bilal, Liu, Hongbin, Zhang, Jingjing, Busayavalasa, Kiran, Risal, Sanjiv, Shao, Jingchen, Satyanarayana, Ande, Coppola, Vincenzo, Tessarollo, Lino, Singh, Meenakshi, Zheng, Chunwei, Han, Chunsheng, Chen, Zijiang, Kaldis, Philipp, Gustafsson, Jan-Åke, Liu, Kui
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.01.2017
• Subjects: Animals; arrest; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Biological Sciences; Cdk2; Cell Cycle Proteins - deficiency; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; cell-cycle regulator; Cells; Chemical Sciences; Chromosomes; Cyclin-Dependent Kinase 2 - chemistry; Cyclin-Dependent Kinase 2 - metabolism; Cyclin-dependent kinases; dynamics; Enzyme Activation; Female; germ cells; Kemi; localization; Male; mammalian meiosis; Medicin och hälsovetenskap; meiosis; Meiotic Prophase I - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Envelope - metabolism; oocytes; Oocytes - cytology; Oocytes - metabolism; proliferation; protein; Protein Interaction Domains and Motifs; Rodents; Science & Technology - Other Topics; Speedy A; Spermatocytes - cytology; Spermatocytes - metabolism; telomere; Telomere - metabolism; Speedy A; meiosis; germ cells; Cdk2; telomere
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1618465114

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.