Characterization of MCM8/9 in DNA repair.

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dc.contributor.advisorTrakselis, Michael A.
dc.creatorMcKinzey, David Reno, 1995-
dc.creator.orcid0000-0003-0845-5352
dc.date.accessioned2023-11-07T14:21:53Z
dc.date.available2023-11-07T14:21:53Z
dc.date.created2023-05
dc.date.issuedMay 2023
dc.date.submittedMay 2023
dc.date.updated2023-11-07T14:21:53Z
dc.description.abstractMCM8 and MCM9 are recent additions to the minichromosomal maintenance family (MCM) of DNA helicases. While not directly implicated in replication, they show both a protective role in aiding the replication fork and assisting in various aspects of DNA repair. The previously uncharacterized C-terminal extension of MCM9 serves vital roles directing the MCM8/9 complex to the nucleus using a bipartite-like nuclear localization sequence (NLS) and promoting interacts with RAD51 through an identified BRC variant (BRCv) motif. Loss of MCM8/9 slows the overall replication speed resulting from more transient fork reversal, lack of protection of the nascent strand, and ultimately double strand breaks. Finally, enzymatic and structural characterization of MCM8/9 reveals a clear affinity for ssDNA containing substrates, stable protection from nucleases, DNA stimulated ATPase activity, and a preferred unwinding orientation. Using cryo-EM, a Walker B mutant version of the MCM8/9 complex shows the overall hexameric structure with the strong density for the C-terminal ATPase domain bound to nucleotide. Altogether this work shows the structure/function activity of the MCM8/9 complex for a more complete understanding of the importance and impact of this complex to maintain genomic integrity during DNA replication.
dc.format.mimetypeapplication/pdf
dc.identifier.uri
dc.identifier.urihttps://hdl.handle.net/2104/12501
dc.language.isoEnglish
dc.rights.accessrightsNo access – contact librarywebmaster@baylor.edu
dc.titleCharacterization of MCM8/9 in DNA repair.
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentBaylor University. Dept. of Chemistry & Biochemistry.
thesis.degree.grantorBaylor University
thesis.degree.namePh.D.
thesis.degree.programChemistry
thesis.degree.schoolBaylor University

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