Role of TLS Polymerases in Replication of DNA Lesions in Human Cells

dc.contributor.advisorLee, James C
dc.contributor.committeeMemberPrakash, Louise
dc.contributor.committeeMemberPrakash, Satya
dc.contributor.committeeMemberWillis, Maurice
dc.contributor.committeeMemberPapaconstantinou, John
dc.contributor.committeeMemberFox, Robert
dc.creatorConde Fabela, Juan A
dc.creator.orcid0000-0003-3252-2463
dc.date.accessioned2021-04-21T15:58:43Z
dc.date.available2021-04-21T15:58:43Z
dc.date.created2016-05
dc.date.submittedMay 2016
dc.date.updated2021-04-21T15:58:44Z
dc.description.abstractCells are constantly exposed to numerous genotoxic lesions that inhibit replication. The inability of cells to correctly repair these lesions results in mutations or chromosomal aberrations that threaten the integrity of the genome. DNA damage tolerance mechanisms, including translesion synthesis (TLS), alleviate this block at the expense of increasing mutagenesis. Minor groove DNA lesions result from lipid peroxidation or exposure to environmental pollutants. Prevalent among these lesions are those produced by tobacco products, particularly benzo(a)pyrene-diolepoxide (BPDE), a polycyclic aromatic hydrocarbon strongly associated with carcinogenesis, particularly lung cancer. Alkylating lesions result from exposures to endogenous methylating agents and naturally occurring methyl halides. They might interfere with base pairing and are cytotoxic. The long-term goal is to understand the mechanisms by which replication through such ubiquitous lesions occurs in human cells. Tumorigenesis is a multistep process associated with accumulation of mutations. Understanding of the biochemical basis of lesion bypass and the role of TLS polymerases will result in insights on how human cells handle exposure to environmental carcinogens and how the TLS processes contribute to cancer avoidance or to cancer risk.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/2152.3/11292
dc.subjectTLS, BPDE, 1MeA, Benzo(a)pyrene
dc.titleRole of TLS Polymerases in Replication of DNA Lesions in Human Cells
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentBiochemistry and Molecular Biology
thesis.degree.grantorThe University of Texas Medical Branch at Galveston
thesis.degree.levelDoctoral
thesis.degree.nameBiochemistry and Molecular Biology (Doctoral)

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