ArticleDevelopmental cell2020
GCNA Preserves Genome Integrity and Fertility Across Species.
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Article in Developmental cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48citing papers in PubMed
3.9field-weighted citation impact, top 5% of its field
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48 citing papers in PubMed, 71 citations in OpenAlex.
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- A non-proteolytic release mechanism for HMCES-DNA-protein crosslinks.The EMBO journal · 2023Article
- GCNA is a histone binding protein required for spermatogonial stem cell maintenance.Nucleic acids research · 2023Article
- DNA repair, recombination, and damage signaling.Genetics · 2022Review
- Divergence of X-linked trans regulatory proteins and the misexpression of gene targets in sterile Drosophila pseudoobscura hybrids.BMC genomics · 2022Article
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Authors and funding
17 authors at 7 institutions in 2 countries.
Varsha BhargavaDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Courtney D GoldsteinDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Logan RussellMagee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, PA 15213, USA.
Lin XuQuantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Murtaza AhmedDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Wei LiMagee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, PA 15213, USA; Tsinghua University MD Program, School of Medicine, Tsinghua University, Haidian District, Beijing 100084, PR China.
Amanda CaseyDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Kelly ServageDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, 6000 Harry Hines Boulevard NA5.120F, Dallas, TX 75235, USA.
Rahul KolliparaMcDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Zachary PicciarelliMagee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, PA 15213, USA.
Ralf KittlerMcDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Alexander YatsenkoMagee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, PA 15213, USA.
Michelle CarmellCold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Biological Sciences, Wellesley College, Wellesley, MA 02481, USA.
Kim OrthDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, 6000 Harry Hines Boulevard NA5.120F, Dallas, TX 75235, USA.
James F AmatrudaDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: jamatruda@chla.usc.edu.
Judith L YanowitzMagee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, PA 15213, USA. Electronic address: yanowitzjl@mwri.magee.edu.
Michael BuszczakDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: michael.buszczak@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · USMagee-Womens Research Institute · USSouthwestern Medical Center · USUniversity of Pittsburgh · USHoward Hughes Medical Institute · USTsinghua University · CNUniversity of Massachusetts Chan Medical School · US
Funding
ZDS2P REGULATES SWE1P-DEPENDENT POLARIZED CELL GROWTH IN S CEREVISIAEP41RR011823 · NCRR · UNIVERSITY OF WASHINGTON · PI DAVIS, TRACY · 1996 to 2011
$24.7MProject IIIP50HD096723 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DONALD F. CONRAD · 2019 to 2026
$15.0MEnhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Ann E. Rougvie · 2012 to 2026
$7.5MDIVISION OF CELL &MOLECULAR BIOLOGY TRAINING PROGRAMT32GM008203 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI COBB, MELANIE H. · 1987 to 2018
$7.0MUnderstanding the architecture, regulation, and function of piRNA-producing genesP01HD078253 · NICHD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI THEURKAUF, WILLIAM EDWARD · 2015 to 2019
$6.5MRNA MEDIATED GENETIC INTERFERENCE IN C ELEGANSR01GM058800 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MELLO, CRAIG C · 1999 to 2014
$4.6MRNA Mediated Genetic Interference in C. elegansR37GM058800 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MELLO, CRAIG C · 2015 to 2024
$3.7MUndergraduate Summer Research Supplement for 5R01GM104007-07: Characterization of a Meiotic Crossover Surveillance SystemR01GM104007 · NIGMS · MAGEE-WOMEN'S RES INST AND FOUNDATION · PI YANOWITZ, JUDITH L · 2013 to 2021
$2.6MCELL POLARITY SIGNALING IN C ELEGANS EMBRYOSR01HD036247 · NICHD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MELLO, CRAIG C · 1999 to 2008
$2.2MRole of GCNA in preserving genome integrity and fertilityR01GM127569 · NIGMS · MAGEE-WOMEN'S RES INST AND FOUNDATION · PI BUSZCZAK, MICHAEL, YANOWITZ, JUDITH L · 2019 to 2022
$2.0MSystematic Characterization of an Aging Stem Cell NicheR01AG047318 · NIA · UT SOUTHWESTERN MEDICAL CENTER · PI BUSZCZAK, MICHAEL · 2015 to 2019
$1.7MDecoding Stem Cell Chromatin Using DrosophilaR01GM086647 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI BUSZCZAK, MICHAEL · 2009 to 2013
$1.5MNCI NIH HHS R13 CA117393NCRR NIH HHS P41 RR011823NIA NIH HHS R01 AG047318NICHD NIH HHS F32 HD008715NICHD NIH HHS P01 HD078253NICHD NIH HHS P50 HD096723NICHD NIH HHS R01 HD036247NIGMS NIH HHS R01 GM058800NIGMS NIH HHS R01 GM086647NIGMS NIH HHS R01 GM104007NIGMS NIH HHS R01 GM125812NIGMS NIH HHS R01 GM127569NIGMS NIH HHS R37 GM058800NIGMS NIH HHS T32 GM008203NIH HHS P40 OD010440NIH HHS S10 OD020103
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.
Indexed as
DNA DamageDNA RepairDNA ReplicationFertilityGenomic InstabilityAnimalsCaenorhabditis elegansDNA Copy Number VariationsDrosophila melanogasterFemaleGenomeGerm CellsHumansMaleNeoplasms, Germ Cell and EmbryonalNuclear ProteinsNuclear ProteinsPeptide Hydrolasesacidic repeat containingACRCchromosome instabilitychromosome segregationDNA-protein crosslinkDNA repairgerm cellintrinsically disordered regionSprT domaintransgenerational inheritance
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