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Speedy A governs non-homologous XY chromosome desynapsis as a unique prerequisite for XY loop-axis organization

Liu, Dongteng ; Zhang, Yuxiang ; Li, Dongliang ; Jiang, Binjie ; Zhao, Xudong ; Li, Yanyan ; Lin, Zexiong ; Zhao, Yu ; Hu, Zhe and Deng, Shuzi , et al. (2025) In EMBO Journal p.1-28
Abstract

In mouse early pachytene spermatocytes, the X and Y chromosomes undergo rapid non-homologous (NH) synapsis and desynapsis, but the functional significance remains unknown. Here, we report that pachynema-specific knockout of Speedy A (SpdyA) from telomeres caused persistent Y-X NH synapsis, with the entire Y axis synapsed onto the X axis. This persistent Y-X NH synapsis did not interrupt meiotic sex chromosome inactivation, recombination, or sex body formation, but it disrupted X-Y loop-axis organization and homologous X-Y desynapsis, leading to spermatocyte death. Similarly, persistent Y-X NH synapsis was also observed in pachytene spermatocytes lacking TRF1, where SpdyA was frequently lost from the X-Y non-pseudoautosomal region... (More)

In mouse early pachytene spermatocytes, the X and Y chromosomes undergo rapid non-homologous (NH) synapsis and desynapsis, but the functional significance remains unknown. Here, we report that pachynema-specific knockout of Speedy A (SpdyA) from telomeres caused persistent Y-X NH synapsis, with the entire Y axis synapsed onto the X axis. This persistent Y-X NH synapsis did not interrupt meiotic sex chromosome inactivation, recombination, or sex body formation, but it disrupted X-Y loop-axis organization and homologous X-Y desynapsis, leading to spermatocyte death. Similarly, persistent Y-X NH synapsis was also observed in pachytene spermatocytes lacking TRF1, where SpdyA was frequently lost from the X-Y non-pseudoautosomal region (non-PAR) telomeres. Mechanistic studies revealed that Serine 48 of SUN1 is a key SpdyA/CDK2 phosphorylation site required for Y-X NH desynapsis. We propose that SpdyA governs Y-X NH desynapsis by stabilizing the linkage between the X-Y non-PAR telomeres and their LINC complexes, and that this process is regulated independently from other aspects of pachynema progression. Our findings suggest a key role for Y-X NH desynapsis in establishing proper X-Y loop-axis organization.

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organization
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type
Contribution to journal
publication status
epub
subject
in
EMBO Journal
pages
1 - 28
publisher
Oxford University Press
external identifiers
  • pmid:40826181
ISSN
1460-2075
DOI
10.1038/s44318-025-00528-8
language
English
LU publication?
yes
additional info
© 2025. The Author(s).
id
80548d02-079d-46df-bc23-6f589c7ebdab
date added to LUP
2025-08-22 08:13:57
date last changed
2025-08-25 08:13:58
@article{80548d02-079d-46df-bc23-6f589c7ebdab,
  abstract     = {{<p>In mouse early pachytene spermatocytes, the X and Y chromosomes undergo rapid non-homologous (NH) synapsis and desynapsis, but the functional significance remains unknown. Here, we report that pachynema-specific knockout of Speedy A (SpdyA) from telomeres caused persistent Y-X NH synapsis, with the entire Y axis synapsed onto the X axis. This persistent Y-X NH synapsis did not interrupt meiotic sex chromosome inactivation, recombination, or sex body formation, but it disrupted X-Y loop-axis organization and homologous X-Y desynapsis, leading to spermatocyte death. Similarly, persistent Y-X NH synapsis was also observed in pachytene spermatocytes lacking TRF1, where SpdyA was frequently lost from the X-Y non-pseudoautosomal region (non-PAR) telomeres. Mechanistic studies revealed that Serine 48 of SUN1 is a key SpdyA/CDK2 phosphorylation site required for Y-X NH desynapsis. We propose that SpdyA governs Y-X NH desynapsis by stabilizing the linkage between the X-Y non-PAR telomeres and their LINC complexes, and that this process is regulated independently from other aspects of pachynema progression. Our findings suggest a key role for Y-X NH desynapsis in establishing proper X-Y loop-axis organization.</p>}},
  author       = {{Liu, Dongteng and Zhang, Yuxiang and Li, Dongliang and Jiang, Binjie and Zhao, Xudong and Li, Yanyan and Lin, Zexiong and Zhao, Yu and Hu, Zhe and Deng, Shuzi and Li, Zheng and Lu, Haonan and Chan, Karen K L and Yeung, William S B and Kaldis, Philipp and Yao, Chencheng and Wang, Hengbin and Chow, Louise T and Liu, Kui}},
  issn         = {{1460-2075}},
  language     = {{eng}},
  month        = {{08}},
  pages        = {{1--28}},
  publisher    = {{Oxford University Press}},
  series       = {{EMBO Journal}},
  title        = {{Speedy A governs non-homologous XY chromosome desynapsis as a unique prerequisite for XY loop-axis organization}},
  url          = {{http://dx.doi.org/10.1038/s44318-025-00528-8}},
  doi          = {{10.1038/s44318-025-00528-8}},
  year         = {{2025}},
}