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

Zhaowei Tu, Mustafa Bilal Bayazit, Hongbin Liu, Jingjing Zhang, Kiran Busayavalasa, Sanjiv Risal, Jingchen Shao, Ande Satyanarayana, Vincenzo Coppola, Lino Tessarollo, Meenakshi Singh, Chunwei Zheng, Chunsheng Han, Zijiang Chen, Philipp Kaldis, Jan Åke Gustafsson, Kui Liu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)592-597
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number3
DOIs
StatePublished - Jan 17 2017

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Prophase
Nuclear Envelope
Telomere
Meiotic Prophase I
Chromosome Pairing
Germ Cells
Cyclin-Dependent Kinases
Homologous Recombination

Keywords

  • Cdk2
  • Germ cells
  • Meiosis
  • Speedy A
  • Telomere

ASJC Scopus subject areas

  • General

Cite this

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

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 3, 17.01.2017, p. 592-597.

Research output: Contribution to journalArticle

Tu, Z, Bayazit, MB, Liu, H, Zhang, J, Busayavalasa, K, Risal, S, Shao, J, Satyanarayana, A, Coppola, V, Tessarollo, L, Singh, M, Zheng, C, Han, C, Chen, Z, Kaldis, P, Gustafsson, JÅ & Liu, K 2017, 'Speedy A-Cdk2 binding mediates initial telomere-nuclear envelope attachment during meiotic prophase i independent of Cdk2 activation', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 3, pp. 592-597. https://doi.org/10.1073/pnas.1618465114
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. / Speedy A-Cdk2 binding mediates initial telomere-nuclear envelope attachment during meiotic prophase i independent of Cdk2 activation. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 3. pp. 592-597.
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AU - Tu, Zhaowei

AU - Bayazit, Mustafa Bilal

AU - Liu, Hongbin

AU - Zhang, Jingjing

AU - Busayavalasa, Kiran

AU - Risal, Sanjiv

AU - Shao, Jingchen

AU - Satyanarayana, Ande

AU - Coppola, Vincenzo

AU - Tessarollo, Lino

AU - Singh, Meenakshi

AU - Zheng, Chunwei

AU - Han, Chunsheng

AU - Chen, Zijiang

AU - Kaldis, Philipp

AU - Gustafsson, Jan Åke

AU - Liu, Kui

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N2 - 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.

AB - 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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