Ubiquitin ligase Huwe1 is essential for spermatogonial development

What is it about?

In the testis, millions of sperm are produced every day. This tremendous replenishing power is support by the spermatogonia, a heterogeneous population that consists of the stem cells and committed progenitors. The cellular protein machinery plays critical roles in many processes in the stem cell. Various modifications of the protein machinery can regulate these processes. A key modification is ubiquitination which can regulate both the turnover and activity of proteins. In this study, we described the essential role of the ubiquitin ligase Huwe1 in spermatogonial development.

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Why is it important?

Spermatogonia are the foundation of sperm production. Defects in spermatogonia perturb spermatogenesis and lead to infertility. Importantly, spermatogonia carry the inheritable genome that should be precisely regulated to allow both genetic variations as well as maintenance of genome integrity. Hitherto, the mechanisms underlying the establishment and maintenance of spermatogonia and the germline DNA damage response under normal conditions was largely unknown. Our study has revealed that the ubiquitin ligase Huwe1 plays a key role by promoting the loss of histone variant H2Ax, thereby suppressing/resolving the DNA damage response associated with spermatogonial development.

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