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CHEMICAL BIOLOGY OF DNA AND RNA ALKYLATION

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Principal Investigator: Wang, Yinsheng
Institute Receiving Award University Of California Riverside
Location Riverside, CA
Grant Number R35ES031707
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 12 Jun 2020 to 31 Mar 2028
DESCRIPTION (provided by applicant): ABSTRACT Alkylating agents are ubiquitously present in the environment, and they can alkylate DNA and RNA directly or after metabolic activation. The focus of the present R35 application is placed on the chemistry and biology of DNA and RNA alkylation, with the overarching goal of understanding the molecular mechanisms through which alkylating agents and other environmental chemicals exert their adverse human health effects. In particular, we will examine the roles of translesion synthesis DNA polymerases in the transcriptional bypass of DNA lesions in cultured human cells, identify DNA damage recognition proteins for alkylated DNA lesions, and investigate their roles in DNA damage response signaling and repair. We will also assess the implications of RNA methylation in the molecular pathology of trinucleotide repeat expansion diseases. The proposed research is a culmination of our established expertise in the areas of DNA damage and repair, proteomics and epitranscriptomics. Completion of the proposed research will lead to an unprecedented level of understanding about the human health consequences of exposure to alkylating agents and other environmental toxicants, and will ultimately result in approaches for the prevention and mitigation of adverse human health consequences arising from environmental exposure.
Science Code(s)/Area of Science(s) Primary: 09 - Genome Integrity
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications See publications associated with this Grant.
Program Officer Frederick Tyson
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