<br/>Accurate replication and transcription of DNA depends on the structural integrity of DNA bases in the human genome. Chemicals from the diet and environment, as well as chemotherapeutic drugs can alter the chemical structure of DNA leading to cell death or the acquisition of mutations. Despite a strong relationship between DNA damage and adverse cellular events, the complexity of biochemical processes linking key cellular events limits our capacity to predict the likelihood of acquiring mutations resulting from chemical exposures or when cancer cells will develop a capacity to resist chemotherapy. By a synthetic chemical probe-based approached, we have gained new insight concerning precise chemical factors that influence steps in the DNA polymerase-mediated DNA synthesis process and the mechanism by which unstable drug-induced DNA damage products impede the progress of RNA polymerase. Furthermore, these mechanistic approaches have led to strategies for the amplification and detection of DNA within gene sequences for diagnostic purposes. These results provide new insight into how chemically modified bases in DNA alter cell viability on the basis of transcriptional stalling and error-prone DNA replication.

Using synthetic chemical tools to understand how toxic chemicals and drugs interfere with DNA replication and transcription

2019 Fall National Meeting

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