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GCNA Preserves Genome Integrity and Fertility Across Species.

Varsha Bhargava | Courtney D Goldstein | Logan Russell | Lin Xu | Murtaza Ahmed | Wei Li | Amanda Casey | Kelly Servage | Rahul Kollipara | Zachary Picciarelli | Ralf Kittler | Alexander Yatsenko | Michelle Carmell | Kim Orth | James F Amatruda | Judith L Yanowitz | Michael Buszczak
Developmental cell | 2020

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.

Pubmed ID: 31839537

Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: R01 HD036247
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NIA NIH HHS, United States
    Id: R01 AG047318
  • Agency: NICHD NIH HHS, United States
    Id: P01 HD078253
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM125812
  • Agency: NICHD NIH HHS, United States
    Id: P50 HD096723
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM086647
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM104007
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM127569
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008203
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM058800
  • Agency: NCI NIH HHS, United States
    Id: R13 CA117393
  • Agency: NIH HHS, United States
    Id: S10 OD020103
  • Agency: NCRR NIH HHS, United States
    Id: P41 RR011823
  • Agency: NIGMS NIH HHS, United States
    Id: R37 GM058800

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Caenorhabditis Genetics Center (tool)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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Zebrafish International Resource Center (tool)

RRID:SCR_005065

Center that supplies access to wild-type, mutant, and transgenic zebrafish lines, EST's/cDNAs, antibodies and fish health services. ZIRC Health Services include diagnostic pathology testing for zebrafish and other small laboratory fish species.

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FastQC (tool)

RRID:SCR_014583

Quality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.

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CRISPOR (tool)

RRID:SCR_015935

Web application that helps design, evaluate and clone guide sequences for the CRISPR/Cas9 system. This sgRNA design tool assists with guide selection in a variety of genomes and pre-calculated results for all human coding exons as a UCSC Genome Browser track.

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Mouse Anti-Drosophila adducin-related protein Monoclonal Antibody, Unconjugated (antibody)

RRID:AB_528070

This monoclonal targets Mouse Drosophila adducin-related protein

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WIK (organism)

RRID:ZIRC_ZL84

Danio rerio with name from ZIRC.

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S2R+ (cell line)

RRID:CVCL_Z831

Cell line S2R+ is a Spontaneously immortalized cell line with a species of origin Drosophila melanogaster (Fruit fly)

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w[1118]; Df(3R)Exel6151, P{w[+mC]=XP-U}Exel6151/TM6B, Tb[1] (organism)

RRID:BDSC_7630

Drosophila melanogaster with name w[1118]; Df(3R)Exel6151, P{w[+mC]=XP-U}Exel6151/TM6B, Tb[1] from BDSC.

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Bloomington Drosophila Stock Center (biomaterial supply resource)

RRID:SCR_006457

Collects, maintains and distributes Drosophila melanogaster strains for research. Emphasis is placed on genetic tools that are useful to a broad range of investigations. These include basic stocks of flies used in genetic analysis such as marker, balancer, mapping, and transposon-tagging strains; mutant alleles of identified genes, including a large set of transposable element insertion alleles; defined sets of deficiencies and a variety of other chromosomal aberrations; engineered lines for somatic and germline clonal analysis; GAL4 and UAS lines for targeted gene expression; enhancer trap and lacZ-reporter strains with defined expression patterns for marking tissues; and a collection of transposon-induced lethal mutations.

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Df(1)BSC719, P+PBac{w[+mC]=XP3.WH3}BSC719 w[1118]/FM7h/Dp(2;Y)G, P{w[+mC]=hs-hid}Y (organism)

RRID:BDSC_26571

Drosophila melanogaster with name Df(1)BSC719, P+PBac{w[+mC]=XP3.WH3}BSC719 w[1118]/FM7h/Dp(2;Y)G, P{w[+mC]=hs-hid}Y from BDSC.

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w[*]; P{w[+mC]=His2Av-mRFP1}II.2 (organism)

RRID:BDSC_23651

Drosophila melanogaster with name w[*]; P{w[+mC]=His2Av-mRFP1}II.2 from BDSC.

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