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

Authors:
Open Access
Publisher website
Google Scholar
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 (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.
Funding Information
  • Science and Technology Planning Project of Shenzen Municipality (SGDX20230821091501011)
  • Shenzhen Science and Technology Innovation Program (KQTD20190929172749226)
  • National Natural Science Foundation of China (NSFC-VR 8211101255)
  • National Key Research and Development Program of China (2022YFC2702701)
  • Sanming Project of Medicine in Shenzen Municipality (SZSM 202211014)

This publication has 45 references indexed in Scilit: