Proteasome Subunit α4s is Essential for Meiotic DNA Repair, Meiosis and Fertility in Male

Abstract

Meiosis, which produces haploid progeny, is critical to ensuring both faithful genome transmission and genetic diversity. The atypical proteasomes, which contain the activator PA200, catalyze the acetylation-dependent degradation of the core histones during spermiogenesis and somatic DNA repair. We show here that the testis-specific proteasome subunit α4s/PSMA8 is essential for male fertility by promoting formation of the properly-assembled spermatoproteasomes, which harbor both PA200 and regular catalytic subunits. α4s stimulated proteasomal degradation of the acetylated core histones in the presence of PA200. Deletion of α4s blocked degradation of the core histones at DNA damage loci and meiotic DNA repair, leading to meiotic arrest at metaphase I in spermatocytes. Thus, α4s is essential for meiotic DNA repair, meiosis and fertility in male at least partially by promoting histone degradation. These results are important for understanding male infertility, and might provide potential targets for male contraception or treatment of male infertility.