Computational evaluation of nucleotide insertion opposite expanded and widened DNA by the translesion synthesis polymerase Dpo4

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dc.contributor.authorAlbrecht, Laura
dc.contributor.authorWilson, Katie A.
dc.contributor.authorWetmore, Stacey D.
dc.date.accessioned2016-07-07T22:20:55Z
dc.date.available2016-07-07T22:20:55Z
dc.date.issued2016
dc.descriptionOpen accessen_US
dc.description.abstractExpanded (x) and widened (y) deoxyribose nucleic acids (DNA) have an extra benzene ring incorporated either horizontally (xDNA) or vertically (yDNA) between a natural pyrimidine base and the deoxyribose, or between the 5- and 6-membered rings of a natural purine. Far-reaching applications for (x,y)DNA include nucleic acid probes and extending the natural genetic code. Since modified nucleobases must encode information that can be passed to the next generation in order to be a useful extension of the genetic code, the ability of translesion (bypass) polymerases to replicate modified bases is an active area of research. The common model bypass polymerase DNA polymerase IV (Dpo4) has been previously shown to successfully replicate and extend past a single modified nucleobase on a template DNA strand. In the current study, molecular dynamics (MD) simulations are used to evaluate the accommodation of expanded/widened nucleobases in the Dpo4 active site, providing the first structural information on the replication of (x,y)DNA. Our results indicate that the Dpo4 catalytic (palm) domain is not significantly impacted by the (x,y)DNA bases. Instead, the template strand is displaced to accommodate the increased C1’–C1’ base-pair distance. The structural insights unveiled in the present work not only increase our fundamental understanding of Dpo4 replication, but also reveal the process by which Dpo4 replicates (x,y)DNA, and thereby will contribute to the optimization of high fidelity and efficient polymerases for the replication of modified nucleobases.en_US
dc.description.peer-reviewYesen_US
dc.identifier.citationAlbrecht, L., Wilson, K.A., & Wetmore, S.D. (2016). Computational evaluation of nucleotide insertion opposite expanded and widened DNA by the translesion synthesis polymerase Dpo4. Molecules, 21. doi:10.3390/molecules21070822en_US
dc.identifier.urihttps://hdl.handle.net/10133/4558
dc.language.isoen_CAen_US
dc.publisherM D P I A Gen_US
dc.publisher.departmentDepartment of Chemistry & Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.subjectExpanded DNAen_US
dc.subjectxDNAen_US
dc.subjectWidened DNAen_US
dc.subjectyDNAen_US
dc.subjectDNA replicationen_US
dc.subjectTranslesion synthesisen_US
dc.subjectBypass polymeraseen_US
dc.subjectDpo4en_US
dc.subjectMolecular dynamicsen_US
dc.titleComputational evaluation of nucleotide insertion opposite expanded and widened DNA by the translesion synthesis polymerase Dpo4en_US
dc.typeArticleen_US
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