GCNA: Guardian of the Genome

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dc.contributor.advisorAbrams, John M.en
dc.contributor.committeeMemberBuszczak, Michaelen
dc.contributor.committeeMemberBrekken, Rolf A.en
dc.contributor.committeeMemberOlson, Eric N.en
dc.creatorGoldstein, Courtney DaVeeen
dc.creator.orcid0000-0002-5409-3463
dc.date.accessioned2022-06-22T22:03:04Z
dc.date.available2022-06-22T22:03:04Z
dc.date.created2020-05
dc.date.issued2020-05-01T05:00:00.000Z
dc.date.submittedMay 2020
dc.date.updated2022-06-22T22:03:05Z
dc.description.abstractThe propagation of species depends on the ability of germ cells to protect their genome in the face of numerous exogenous and endogenous threats. While germ cells employ a number of know repair pathways, specialized mechanisms that ensure high-fidelity replication, chromosome segregation, and repair of germ cell genomes remain incompletely understood. Here, we identify 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 a second SprT domain protein Spartan. Structural analysis reveals that while the SprT domain is needed to limit meiotic and replicative damage, much of GCNA's function maps to its IDR. This work shows GCNA protects germ cells from various sources of damage, providing novel insights into conserved mechanisms that promote genome integrity across generations.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1333220384
dc.identifier.urihttps://hdl.handle.net/2152.5/9870
dc.language.isoenen
dc.subjectFertilityen
dc.subjectGenomic Instabilityen
dc.subjectNuclear Proteinsen
dc.subjectPeptide Hydrolasesen
dc.subjectDNA Damageen
dc.subjectDNA Repairen
dc.subjectDNA Replicationen
dc.titleGCNA: Guardian of the Genomeen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineGenetics and Developmenten
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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