Zhaowei Tua,1, Mustafa Bilal Bayazita,1, Hongbin Liub, Jingjing Zhanga, Kiran Busayavalasaa, Sanjiv Risala,
Jingchen Shaoa, Ande Satyanarayanac,2,3, Vincenzo Coppolac4, Lino Tessarolloc, Meenakshi Singha, Chunwei Zhengd, Chunsheng Hand, Zijiang Chenb, Philipp Kaldise,f,5, Jan-Åke Gustafssong5, and Kui Liua,b,5
a Department of Chemistry and Molecular Biology, University of Gothenburg, SE-40530 Gothenburg, Sweden;
b The Key Laboratory of Reproductive
Endocrinology, Shandong University, Ministry of Education, Jinan 250001, China;
c Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201;
d State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;
e Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore 138673, Republic of Singapore;
f Department of Biochemistry, National University of Singapore, Singapore 117599, Republic of Singapore; and
g Center for Nuclear
Receptors and Cell Signaling, University of Houston, Houston, TX 77204
Published in Proc. Natl. Acad. Sci. USA on 17 January 2017.
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.
Figure Legend : Speedy A is localized to telomeres in structurally preserved spermatocytes during meiotic prophase I. Immunofluorescent staining of structurally preserved PD18 wild-type spermatocytes. Telomeres were stained with TRF1. (A–C) In preleptotene cells, Speedy A was only detected on telomeres that were on the NE (arrows). Telomeres inside the nucleus lacked the Speedy A signal
(arrowheads). (D–L) In leptotene, zygotene, and pachytene cells, Speedy A and TRF1 signals overlapped on telomeres (arrows).
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