DNA tennplates for transcription are continuously damaged by extrinsic factors such as radiation and chemical agents, as well as by products of endogenous metabolic processes. Maintenance of DNA integrity and high fidelity in transcription are crucial for life processes. DNA damage impairs transcription and triggers a variety of cellular responses, including DNA repair pathways, signaling pathways that activate cell cycle checkpoints, apoptosis, transcription, and chromatin remodeling. Defects in DNA repair or the processing of DNA damage can lead to cancer or other human diseases. It is inevitable for RNA polymerases to encounter DNA damage during transcription. Certain types of DNA lesions allow RNA polymerase bypass, while others completely block transcription. RNA polymerase 11 (pol II) bypass frequently results in mutagenesis at RNA, generating mutant proteins. In contrast, arrest of pol II by DNA lesions signals a specific DNA repair pathway to correct the damage and maintain the integrity ofthe DNA. The goal of my research is to understand the mechanisms of these cellular DNA damage processing pathways through an integrated multidisciplinary combination of chemical, structural, biochemical, and molecular biological methods.

Public Health Relevance

This knowledge will provide us strutural insights for transcriptional fidelity control, DNA damage recognition and DNA repair. In addition, this konowledge will have implications for rational drug design for cancer and other transcription related human diseases.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Transition Award (R00)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Program Officer
Flicker, Paula F
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
Schools of Pharmacy
La Jolla
United States
Zip Code
Walmacq, Celine; Wang, Lanfeng; Chong, Jenny et al. (2015) Mechanism of RNA polymerase II bypass of oxidative cyclopurine DNA lesions. Proc Natl Acad Sci U S A 112:E410-9
Wang, Lanfeng; Limbo, Oliver; Fei, Jia et al. (2014) Regulation of the Rhp26ERCC6/CSB chromatin remodeler by a novel conserved leucine latch motif. Proc Natl Acad Sci U S A 111:18566-71
Xu, Liang; Chen, Ying-Chu; Nakajima, Satoshi et al. (2014) A Chemical Probe Targets DNA 5-Formylcytosine Sites and Inhibits TDG Excision, Polymerases Bypass, and Gene Expression. Chem Sci 5:567-574
Silva, Daniel-Adriano; Weiss, Dahlia R; Pardo Avila, Fátima et al. (2014) Millisecond dynamics of RNA polymerase II translocation at atomic resolution. Proc Natl Acad Sci U S A 111:7665-70
Zhang, Su; Wang, Dong (2013) Understanding the Molecular Basis of RNA Polymerase II Transcription. Isr J Chem 53:
Kellinger, Matthew W; Park, Ga Young; Chong, Jenny et al. (2013) Effect of a monofunctional phenanthriplatin-DNA adduct on RNA polymerase II transcriptional fidelity and translesion synthesis. J Am Chem Soc 135:13054-61
Da, Lin-Tai; Pardo Avila, Fátima; Wang, Dong et al. (2013) A two-state model for the dynamics of the pyrophosphate ion release in bacterial RNA polymerase. PLoS Comput Biol 9:e1003020
Da, Lin-Tai; Wang, Dong; Huang, Xuhui (2012) Dynamics of pyrophosphate ion release and its coupled trigger loop motion from closed to open state in RNA polymerase II. J Am Chem Soc 134:2399-406
Kellinger, Matthew W; Song, Chun-Xiao; Chong, Jenny et al. (2012) 5-formylcytosine and 5-carboxylcytosine reduce the rate and substrate specificity of RNA polymerase II transcription. Nat Struct Mol Biol 19:831-3
Kellinger, Matthew W; Ulrich, Sebastien; Chong, Jenny et al. (2012) Dissecting chemical interactions governing RNA polymerase II transcriptional fidelity. J Am Chem Soc 134:8231-40

Showing the most recent 10 out of 14 publications