Meiosis, which produces haploid progeny, is critical to ensuring both faithful genome transmission and genetic diversity. Proteasomes play critical roles at various stages of spermatogenesis, including meiosis, but the underlying mechanisms remain unclear. The atypical proteasomes, which contain the activator PA200, catalyze the acetylation-dependent degradation of the core histones in elongated spermatids and DNA repair in somatic cells. We show here that the testis-specific proteasome subunit α4s/PSMA8 is essential for male fertility by promoting proper formation of spermatoproteasomes, which harbor both PA200 and constitutive catalytic subunits. Immunostaining of a spermatocyte marker, SYCP3, indicated that meiosis was halted at stage of spermatocytes in the α4s-deficient testes. α4s stimulated the in vitro degradation of the acetylated core histones, instead of non-acetylated histones, by the PA200-proteasome. Deletion of α4s blocked degradation of the core histones at DNA damage loci in spermatocytes, leading to meiotic arrest at metaphase I. Thus, α4s is required for histone degradation at meiotic DNA damage loci, proper progression of meiosis, and fertility in males by promoting proper formation of spermatoproteasomes. These results are important for understanding male infertility, and might provide potential targets for male contraception or treatment of male infertility.

中文翻译：

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蛋白酶体亚基 α4s 对于精母细胞减数分裂 DNA 修复过程中精子蛋白酶体的形成和组蛋白降解至关重要

减数分裂产生单倍体后代，对于确保忠实的基因组传递和遗传多样性至关重要。蛋白酶体在精子发生的各个阶段（包括减数分裂）发挥着关键作用，但其潜在机制仍不清楚。非典型蛋白酶体含有激活剂 PA200，可催化细长精子细胞中核心组蛋白的乙酰化依赖性降解和体细胞中的 DNA 修复。我们在此表明​​，睾丸特异性蛋白酶体亚基 α4s/PSMA8 通过促进精子蛋白酶体的正确形成（包含 PA200 和组成型催化亚基），对于男性生育能力至关重要。精母细胞标记物 SYCP3 的免疫染色表明，在 α4s 缺陷的睾丸中，减数分裂在精母细胞阶段停止。α4s 刺激 PA200 蛋白酶体体外降解乙酰化核心组蛋白，而不是非乙酰化组蛋白。α4s 的缺失阻止了精母细胞 DNA 损伤位点处核心组蛋白的降解，导致减数分裂在中期 I 停滞。因此，α4s 是减数分裂 DNA 损伤位点处的组蛋白降解、减数分裂正常进行以及通过促进适当的雄性生育能力所必需的。精子蛋白酶体的形成。这些结果对于了解男性不育症很重要，并且可能为男性避孕或男性不育症的治疗提供潜在目标。α4s 是减数分裂 DNA 损伤位点处的组蛋白降解、减数分裂的正常进展以及通过促进精子蛋白酶体的正确形成而实现男性生育力所必需的。这些结果对于了解男性不育症很重要，并且可能为男性避孕或男性不育症的治疗提供潜在目标。α4s 是减数分裂 DNA 损伤位点处的组蛋白降解、减数分裂的正常进展以及通过促进精子蛋白酶体的正确形成而实现男性生育力所必需的。这些结果对于了解男性不育症很重要，并且可能为男性避孕或男性不育症的治疗提供潜在目标。