Composition, Assembly, and Dynamics of PML Nuclear Bodies

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dc.contributor.advisorJaqaman, Khulouden
dc.contributor.committeeMemberBanaszynski, Lauraen
dc.contributor.committeeMemberYu, Hongtaoen
dc.contributor.committeeMemberRosen, Michael K.en
dc.creatorRice, Allyson M.en
dc.creator.orcid0000-0002-2781-0439
dc.date.accessioned2023-06-07T18:15:23Z
dc.date.available2023-06-07T18:15:23Z
dc.date.created2021-05
dc.date.issued2021-05-01T05:00:00.000Z
dc.date.submittedMay 2021
dc.date.updated2023-06-07T18:15:24Z
dc.descriptionPages 1-130 are misnumbered as page 2-131.en
dc.description.abstractBiomolecular condensates concentrate biomolecules into two- or three-dimensional foci that lack surrounding membranes and can scale in diameter from tens of nanometers to several microns in cells. Promyelocytic leukemia nuclear bodies (PML NBs) are a biomolecular condensate conserved across mammalian, avian and reptilian species. They are primarily composed of the PML protein, and over two hundred additional proteins have reported associations with PML NBs. While the precise function of PML NBs has remained ambiguous, they have been implicated in diverse cellular pathways, from viral response to epigenetics. Previous studies surrounding PML NBs in cells have been largely qualitative, and the physical mechanisms underlying PML NB assembly, dynamics and composition remain largely unknown. In this thesis, I have used quantitative imaging methods in live cells to elucidate properties of PML NBs in their physiological environment. I identified the role of a PML post translational modification, addition of the small ubiquitin-like modifier (SUMO) at lysine 65, in balancing the composition with the dynamics of PML NBs. Additionally, I discuss PML NB behaviors throughout the cell cycle, investigate client recruitment into PML NBs, and evaluate the contribution of ordered domains in PML in PML NB formation. Finally, I analyzed different models for PML NB assembly and propose future lines of study that could uncover their assembly mechanism. Collectively, my work sheds light on a natural condensate and illustrates the complexity of condensate regulation in vivo.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1381370370
dc.identifier.urihttps://hdl.handle.net/2152.5/10056
dc.language.isoenen
dc.subjectBiomolecular Condensatesen
dc.subjectPromyelocytic Leukemia Nuclear Bodiesen
dc.subjectSumoylationen
dc.subjectTranscription Factorsen
dc.titleComposition, Assembly, and Dynamics of PML Nuclear Bodiesen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineMolecular Biophysicsen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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