Dr. Wang's primary research interests areto understand the fundamental mechanisms of transcription and epigenetic regulation, chromatin remodeling, and DNA repair. His group takes a multidisciplinary approach, combining structural biology, chemical biology, computational biology, biochemical, and genetic methods, to study key protein complexes involved in these processing pathways.
A major direction of his laboratory has been to elucidate the mechanisms by which DNA damage is recognized and repaired during transcription. Specifically, his group is focused on the mechanism of the initiation of transcription-coupled DNA repair (TC-NER), which is an important DNA repair pathway that specifically removes DNA lesions in the transcribed genome. The results will have implications for DNA damage recognition and DNA repair. Moreover, understanding how cell process these DNA lesions will help us to decipher the mechanisms of drug action and resistance and pave the way for rational improvement of novel anticancer drugs.
Research Focus Areas:
Neurodevelopment and Neurodegenerative Disease |
Gene Expression and Regulation | DNA Replication and Repair | Biochemistry and Structural Biology
Wang, D., Bushnell, D. A., Westover, K. D., Kaplan, C. D., Kornberg, R. D.* (2006) Structural Basis of Transcription: Role of the Trigger Loop in Substrate Specificity and Catalysis Cell 127, 941-954. PMCID: PMC1876690.
Wang, D., Bushnell, D. A., Westover, K. D., Huang, X. H., Levitt, M. & Kornberg, R. D.* (2009) Structural Basis of Transcription: Backtracked RNA Polymerase II at 3.4 Å Resolution. Science 324, 1203-1206. PMCID: PMC2718261.
Kellinger, M.W., Ulrich, S., Chong, J., Kool, E.T.*, Wang, D.* (2012) Dissecting Chemical Interactions Governing RNA Polymerase II Transcriptional Fidelity. J. Am. Chem. Soc. 134, 8231-40. PMCID: PMC3367139.
Kellinger, M.W., Song, C., Chong, J., Lu, X., He. C., Wang, D.* (2012)
5-Formyl- and 5-Carboxylcytosine Reduce the Rate and Substrate Specificity of RNA Polymerase II Transcription Nature Struct. Mol. Biol. 19, 831-33. PMCID: PMC3414690.
Wang, L., Zhou, Y., Xu, L., Xiao, R., Lu, X., Chen, L., Chong, J., Li, H., He, C., Fu, X.-D.*, Wang, D.* (2015)
Molecular Basis for 5-Carboxycytosine Recognition by RNA Polymerase II Elongation Complex. Nature 523, 621–625. PMCID: PMC4521995.
Xu, J., Lahiri, I., Wang, W., Wier, A., Cianfrocco, M.A., Chong, J., Hare, A.A., Dervan, P.B., DiMaio, F. Leschziner, A.E*. & Wang, D. *(2017)
Structural Basis for the Initiation of Eukaryotic Transcription-Coupled DNA Repair. Nature 551:653-657. PMCID: PMC5907806.
Wang, W., Xu, J., Limbo, O., Fei, J., Kassavetis, G. A., Chong, C., Kadonaga, J. T., Russell, P., Li, B., Wang, D.* (2019) Molecular Basis of Chromatin Remodeling by Rhp26, A Yeast CSB Ortholog. Proc. Natl. Acad. Sci. USA 116(13):6120-6129. PMCID: PMC6442633.
Tse, C.K.M., Xu, J., Xu, L., Sheong, F.K., Wang, S., Chow, H.Y., Gao, X., Li, X., Cheung, P.*, Wang, D.*, Zhang, Y.*, Huang, X.* (2019) Intrinsic Cleavage of RNA Polymerase II Adopts a Nucleobase-Independent Mechanism Assisted by Transcript Phosphate. Nature Catal. 2:228–235. PMCID: PMC6548511.
Oh, J., Fleming, A.M., Xu, J. Chong, J., Burrows, C.J., & Wang, D.* (2020) RNA Polymerase II Stalls on Oxidative DNA Damage via a "Torsion-Latch" Mechanism Involving Lone Pair-Pi and CH-Pi Interactions. Proc Natl Acad Sci U S A. 117(17): 9338-9348. PMCID: PMC7196775.
Xu, J., Wang, W., Xu, L., Chen, J.Y., Chong, J., Oh, J., Leschziner, A.E., Fu, X.D., and & Wang, D.* (2020) Cockayne Syndrome B Protein Acts as an ATP-Dependent Processivity Factor that Helps RNA Polymerase II Overcome Nucleosome Barriers. Proc Natl Acad Sci U S A. (in press).