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

Artikel i vetenskaplig tidskrift
Författare Z. W. Tu
M. B. Bayazit
H. B. Liu
Jingjing Zhang
Kiran Busayavalasa
Sanjiv Risal
Jingchen Shao
A. Satyanarayana
V. Coppola
L. Tessarollo
M. Singh
Chunwei Zheng
C. S. Han
Z. J. Chen
P. Kaldis
J. A. Gustafsson
Kui Liu
Publicerad i Proceedings of the National Academy of Sciences of the United States of America
Volym 114
Nummer/häfte 3
Sidor 592-597
ISSN 0027-8424
Publiceringsår 2017
Publicerad vid Institutionen för kemi och molekylärbiologi
Sidor 592-597
Språk English
Länkar 10.1073/pnas.1618465114
Ämnesord meiosis, telomere, Speedy A, Cdk2, germ cells, cell-cycle regulator, mammalian meiosis, protein, mice, dynamics, proliferation, localization, chromosomes, oocytes, arrest, Science & Technology - Other Topics
Ämneskategorier Biokemi och molekylärbiologi, Kemi

Sammanfattning

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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