Regulation of Sister Chromatid by the Acetyltransferase Naa50

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dc.contributor.advisorSeemann, Joachimen
dc.contributor.committeeMemberYu, Hongtaoen
dc.contributor.committeeMemberLi, Bingen
dc.contributor.committeeMemberOlson, Eric N.en
dc.creatorRong, Ziyeen
dc.creator.orcid0000-0001-5500-5894
dc.date.accessioned2018-08-24T20:36:37Z
dc.date.available2018-08-24T20:36:37Z
dc.date.created2016-08
dc.date.issued2016-07-25
dc.date.submittedAugust 2016
dc.date.updated2018-08-24T20:31:00Z
dc.description.abstractDuring the cell cycle, sister-chromatid cohesion tethers sister chromatids together from S phase to the metaphase-anaphase transition and ensures accurate chromosome segregation of chromatids into daughter cells. N-terminal acetylation is one of the most prevalent protein covalent modifications in eukaryotes and is mediated by a family of N-terminal acetyltransferases (NAT). Naa50 (also called San or NatE) has previously been shown to play a role in sister-chromatid cohesion in metazoans. The mechanism by which Naa50 contributes to cohesion is not understood, however. Here, I show that depletion of Naa50 in HeLa cells weakens the interaction between cohesin and its positive regulator sororin and causes cohesion defects in interphase, consistent with a role of Naa50 in cohesion establishment or maintenance. Strikingly, co-depletion of NatA, a heterodimeric NAT complex that physically interacts with Naa50, rescues the sister-chromatid cohesion defects and the resulting mitotic arrest caused by Naa50 depletion, indicating that NatA and Naa50 play antagonistic roles in cohesion. Purified recombinant NatA and Naa50 do not affect each other's NAT activity in vitro. Because NatA and Naa50 exhibit distinct substrate specificity, I propose that they modify different effectors and regulate sister-chromatid cohesion in opposing ways.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1049807574
dc.identifier.urihttps://hdl.handle.net/2152.5/5724
dc.language.isoenen
dc.subjectCell Cycle Proteinsen
dc.subjectChromatidsen
dc.subjectChromosomal Proteins, Non-Histoneen
dc.subjectChromosomes, Humanen
dc.subjectMitosisen
dc.subjectN-Terminal Acetyltransferase Aen
dc.subjectN-Terminal Acetyltransferase Een
dc.subjectS Phaseen
dc.titleRegulation of Sister Chromatid by the Acetyltransferase Naa50en
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineCell Regulationen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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