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      GCNA Preserves Genome Integrity and Fertility Across Species

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          Abstract

          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. Bhargava et al . identify GCNA as a critical, conserved germ cell factor that helps to prevent replication stress and DNA-protein crosslink accumulation. Loss of GCNA correlates with increased copy number variation in human germ cell tumors.

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          Author and article information

          Journal
          Developmental Cell
          Developmental Cell
          Elsevier BV
          15345807
          January 2020
          January 2020
          : 52
          : 1
          : 38-52.e10
          Article
          10.1016/j.devcel.2019.11.007
          6946843
          31839537
          f7bfc45c-9837-4c61-ad97-f4d2704f4c88
          © 2020

          https://www.elsevier.com/tdm/userlicense/1.0/

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