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dc.contributor.advisorWilliam Theurkaufen_US
dc.contributor.authorRice, Nicholas P
dc.date.accessioned2023-05-22T15:35:50Z
dc.date.available2023-05-22T15:35:50Z
dc.date.issued2023-03-10
dc.identifier.doi10.13028/0vjk-3031en_US
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52089
dc.description.abstractBarbara Mcclintock proposed the genomic stress hypothesis, which states that transposable element activation is an adaptive response to generate new variation. Transposons are ubiquitous selfish genetic elements that compose a large fraction of eukaryotic genomes. In Drosophila melanogaster’s germline, transposons are regulated by small RNAs called Piwi Interacting RNAs (piRNAs). piRNAs originate from clusters of repeats, whose expression is driven by a germline-specific protein Rhino, and cleavage products produced by Argonaute proteins concentrated in nuage, a phase-separated granule. The “genomic stress” model must operate in the germline, and the effect of stress on the piRNA pathway is not well understood. In my thesis, I investigated how two types of stress, temperature and DNA damage via transposon mobilization, affect the piRNA pathway. We show heat shock rapidly and reversibly disrupts the nuclear biogenesis factors required for piRNA production and the collapse of cluster transcription. This loss and recovery of Rhino and its associated factors allowed us to show that cluster assembly is independent of piRNAs. Mutations in the piRNA pathway upregulate transposons and activate the DNA damage response complicating any single piRNA mutant phenotype. We thus created double mutants with a kinase required for DNA damage signaling (Chk2) and demonstrated that Chk2 signaling alters nuage composition. Stripping away damage signaling revealed that components of the nuclear piRNA pathway are required to link nuage properly to clusters. Together we show that the piRNA pathway responds to stress in different ways and that this differential response is an additional tool for investigating the piRNA pathway.en_US
dc.language.isoen_USen_US
dc.publisherUMass Chan Medical Schoolen_US
dc.rightsCopyright © 2023 Riceen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subjectpiRNAen_US
dc.subjectpiRNA pathwayen_US
dc.subjectHeat Shocken_US
dc.subjectDNA Damageen_US
dc.subjectPIWI-interacting RNAen_US
dc.subjectGenomic Stress Hypothesisen_US
dc.subjectStressen_US
dc.subjectDrosophilaen_US
dc.subjecttransposable elementsen_US
dc.subjecttransposonen_US
dc.subjectGenetics and Genomicsen_US
dc.subjectnuageen_US
dc.subjectpiRNA clustersen_US
dc.subjectGenomic Stressen_US
dc.subjectHeat Stressen_US
dc.subjectGermlineen_US
dc.titleImpact of stress on the piRNA Pathwayen_US
dc.typeDoctoral Dissertationen_US
atmire.contributor.authoremailnicholas.rice@umassmed.eduen_US
dc.contributor.departmentProgram in Molecular Medicineen_US
dc.description.thesisprogramInterdisciplinaryen_US
dc.identifier.orcid0000-0002-9023-6820en_US


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