Dissertation Information for Vladimir BeljanskiNAME:
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SCHOOL: ADVISORS: COMMITTEE MEMBERS: MPACT Status: Fully Complete Title: Biological and biomolecular interactions of crosslinking agents and cisplatin analogs Abstract: Using Saccharomyces cerevisiae ( S. cerevisiae ) DNA damage processing-compromised strains, nucleotide excision repair (NER), recombination repair (RR) and translesion synthesis (TLS) were identified as the pathways responsible for the processing of DNA lesions induced by the DNA-crosslinking anticancer drugs, cisplatin, nitrogen mustard, mitomycine, and carmustine. Processing of these lesions, however, requires substantially different contributions of NER, RR, and TLS. In contrast to the previously held belief, TLS and RR contribute to survival to a greater extent than NER in the processing of cisplatin-DNA lesions. Such knowledge can be used to design effective combinations of therapeutics. For example, nitrogen mustard and carmustine saturate capacity of the pathways even at relatively low concentrations, and act synergistically in the RR-compromised strain. |
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