The propagation of species depends on the ability of germ cells to protect their genome from numerous exogenous and endogenous threats. While these cells employ ubiquitous repair pathways, specialized mechanisms that ensure high-fidelity replication, chromosome segregation, and repair of germ cell genomes remain incompletely understood. We identified Germ Cell Nuclear Acidic Peptidase (GCNA) as a conserved regulator of genome stability in flies, worms, zebrafish, and human germ cell tumors. GCNA contains an acidic intrinsically disordered region (IDR) and a protease-like SprT domain. In addition to chromosomal instability and replication stress, Gcna mutants accumulate DNA-protein crosslinks (DPCs). GCNA acts in parallel with the SprT domain protein Spartan. Structural analysis reveals that while the SprT domain is needed to limit DNA damage, the IDR imparts significant function. This work shows that GCNA protects germ cells from various sources of damage, providing insights into conserved mechanisms that promote genome integrity across generations.

中文翻译：

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GCNA可以保护整个物种的基因组完整性和育性。

物种的繁殖取决于生殖细胞保护其基因组免受众多外源性和内源性威胁的能力。尽管这些细胞采用无处不在的修复途径，但确保高保真复制，染色体分离和修复生殖细胞基因组的专门机制仍未完全了解。我们将生殖细胞核酸性肽酶（GCNA）确定为苍蝇，蠕虫，斑马鱼和人类生殖细胞肿瘤中基因组稳定性的保守调节因子。GCNA包含一个酸性内在无序区（IDR）和一个蛋白酶样SprT域。除了染色体不稳定和复制压力，Gcna突变体还会积累DNA-蛋白质交联（DPC）。GCNA与SprT域蛋白Spartan平行起作用。结构分析表明，尽管需要SprT域来限制DNA损伤，IDR发挥了重要作用。这项工作表明，GCNA保护生殖细胞免受各种损害，从而深入了解了促进世代基因组完整性的保守机制。