In all living systems, genetic information is encoded by a simple chemical code of four major nucleotide bases (A, T, G, and C). However, up to 2% of the nucleobases in our genome are not in their canonical form, but are instead structurally altered. Some of these bases are intentionally modified by cellular enzymes to regulate specific genes; other bases are inadvertently modified as a result of exposure to reactive agents present in our environment to form DNA adducts. For example, cytosine and adenine bases of DNA can be enzymatically methylated and demethylated to regulate gene expression in cells and tissues; this process known as “epigenetics” is essential for normal development, immune response, and DNA repair. On the other hand, unintentional nucleobase modifications (DNA adducts) that occur as a result of environmental exposures such UV light and dietary/environmental chemicals can cause errors during DNA replication, leading to heritable mutations and the development of cancer. Specifically, proteins can become trapped on DNA strands to generate bulky DNA-protein crosslinks. My laboratory investigates both naturally occurring DNA modifications and toxic/mutagenic DNA adducts. In this presentation, I will describe our efforts to identify novel DNA modifications, to elucidate their biological impacts, and to develop ultra-sensitive methodologies for their detection in humans.

Adventures of a chemist in toxicology: DNA adducts, epigenetic deregulation, and proteins trapped on DNA strands

ACS Fall 2021

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