title: Speedy A-Cdk2 binding mediates initial telomere-nuclear envelope attachment during meiotic prophase I independent of Cdk2 activation.
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.
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-40530 Gothenburg, Sweden.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-40530 Gothenburg, Sweden.
authors.forename: Mustafa Bilal
authors.initials: MB
authors.lastname: Bayazit
authors.affiliation: The Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan 250001, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-40530 Gothenburg, Sweden.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-40530 Gothenburg, Sweden.
authors.forename: Kiran
authors.initials: K
authors.lastname: Busayavalasa
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-40530 Gothenburg, Sweden.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Risal
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-40530 Gothenburg, Sweden.
authors.forename: Jingchen
authors.initials: J
authors.lastname: Shao
authors.affiliation: Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201.
authors.forename: Ande
authors.initials: A
authors.lastname: Satyanarayana
authors.affiliation: Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Coppola
authors.affiliation: Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201.
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-40530 Gothenburg, Sweden.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Singh
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Han
authors.affiliation: The Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan 250001, China.
authors.forename: Zijiang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: 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.|Department of Biochemistry, National University of Singapore, Singapore 117599, Republic of Singapore.
authors.forename: Philipp
authors.identifier: 0000-0002-7247-7591
authors.initials: P
authors.lastname: Kaldis
authors.affiliation: 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.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
authors.affiliation: 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.|The Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan 250001, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D008297:Male; D049469:Meiotic Prophase I / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009685:Nuclear Envelope / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism; D016615:Telomere / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C529672:Spy1 protein, mouse; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2
keywords: Cdk2; Speedy A; germ cells; meiosis; telomere