S100PBP interacts with nucleoporin TPR and facilitates XY crossover formation in mice.

During meiosis, at least one crossover is selectively generated per pair of homologous chromosomes through homologous recombination to ensure their faithful segregation. The molecular mechanisms controlling meiotic recombination, particularly in XY chromosomes that share a tiny region of homology (i.e., the pseudoautosomal region, PAR), remain poorly understood. Here, we identify S100PBP as a key modulator of both XY and autosomal recombination in mice. S100pbp-knockout mice exhibit male infertility and spermatogenesis arrest at meiotic metaphase I, resulting from a drastic reduction in XY crossovers. This failure in XY crossover formation is due to a reduction in TEX11/M1AP-bound recombination intermediates at the PAR. By contrast, disruption of S100PBP significantly increases the number of recombination intermediates and crossovers on autosomes. Co-immunoprecipitation mass spectrometry revealed that S100PBP interacts with the nucleoporin TPR. Furthermore, S100PBP is localized specifically to the nuclear pores of meiocytes, likely in a TPR-dependent manner. These findings demonstrate that S100PBP promotes XY crossover formation while limiting excess autosomal crossovers and shed light on the potential role of nuclear pores in regulating meiotic recombination.