- Coordinator INBRE and Professor
- Office: 495E Lab: 450
- Phone: 401.874.5024
- Email: email@example.com
- Office Location: 7 Greenhouse Road, Kingston, RI 02881
Aromatic amines are implicated in the etiology of human cancers. DNA adduct formation is believed to be responsible for initiation of many amine-induced cancers. Hence it is imperative to establish how a cancerous lesion is repaired or replicated at the molecular and atomic levels.
The objective of our work is to identify, characterize, and understand the structural and conformational aspects of the key molecular players that are involved in adverse outcomes such as adduct structures, polymerases, and repair proteins. Our working hypothesis is that aromatic amine lesions exist in equilibrium of certain prototype conformations and that it is their relative population ratios that determine mutational and repair outcomes.
To this end our laboratory has been mapping out lesion-induced conformational heterogeneity. We investigate the impact of sequence dependent heterogeneity not only on nucleotide excision repair and mutation, but also their affinities on repair and polymerase proteins.
We employ various state-of-the-art spectroscopic, calorimetric, gel-and chip-based technologies to study adduct conformation. Such knowledge is essential for developing strategies for drug discovery, prevention and risk assessment. Dr. Cho is also passionate about using 3D printing and animation technology that would help facilitate students’ learning of the molecular mechanisms of drug action.
Cancer, DNA Damage, Repair, Replication, Mutation, DNA-adduct, Molecular Toxicology, Structural Biology, Chemical Biology
Carcinogenesis, NCTR, FDA, Jefferson, AR, 1987-1991
Carcinogenesis, University of Chicago, Chicago, IL, 1985-1987
Ph.D. Medicinal Chemistry, University of Illinois Medical Center, Chicago, IL, 1985
M.S. Organic Chemistry, Yonsei University, Seoul, Korea, 1979
B.S. Chemistry, Yonsei University, Seoul, Korea, 1977
Hilton, S. Gopal, L. Xu, S. Mazumder, P. R. Musich, and B. P. Cho*, Y. Zou.* Dissociation dynamics of XPC-HR23B from damaged DNA is a determining factor of NER efficiency. PLoS, http://dx.doi.org/10.1371/journal.pone.0157784. Published: June 21, 2016
Xu and B. P. Cho.* Conformational Insight on the Mechanism of Acetylaminofluorene-dG induced Frameshifts Mutation in the NarI Mutational Hotspot. Chem.Res.Toxicol. 29, 213-226 (2016).
V. Jain, V. G. Vaidyanathan, S. Patnaik, S. Gopal, and B. P. Cho. Conformational Insights into the Lesion and Sequence Effects for Arylamine-Induced Translesion DNA Synthesis: 19F NMR, Surface Plasmon Resonance, and Primer Kinetic Studies. Biochemistry 53, 4059-71 (2014).
L. Xu, V. G. Vaidyanathan, B. P. Cho, Real-time surface plasmon resonance study of biomolecular interactions between polymerase and bulky mutagenic DNA lesions. Chem. Res. Toxicol. 27, 1796-807 (2014).
V.G Vaidyanathan, F. Liang, W.A. Bread, D. D. Shock, S. H. Wilson and B. P. Cho. * Insights into the Conformation of Aminofluorene-dG Adduct in a DNA Polymerase Active Site. J. Biol. Chem. 23573-85 (2013)
Vaidyanathan, VG, Xu, L, Cho, BP. Probing the binary and ternary binding affinities between Klenow fragment (Kfexo-) and various arylamine DNA lesions by surface plasmon resonance, Chem. Res. Toxicol., 1568 (2013).
Jain, V, Hilton, B, Patnaik, S, Zou, Y, Chiarelli, MP, Cho, BP. Conformational and thermodynamic properties modulate the nucleotide excision repair of 2-aminofluorene and 2-acetylaminofluorene dG adducts in the NarI sequence. Nucleic Acids Res., 1-13 (2012).
Vaidyanathan, VG, Cho, BP. Sequence effects on translesion synthesis of an aminofluorene-DNA adduct: conformational, thermodynamic, and primer extension kinetic studies. Biochemistry, 51, 1983-1995 (2013).
Patnaik, S, Cho, BP. “Structures of 2-acetylaminofluorene modified DNA revisited: insight into conformational heterogeneity.” Chem. Res. Toxicol., 1650-1652 (2010).
Liang, F, Cho, BP. Enthalpy-entropy contribution to carcinogen-induced DNA conformational heterogeneity. Biochemistry 259-266 (2010).
Liang, F, Jain, N, Hutchens, T, Shock, DD, Beard, WA, Wilson, SH, Chiarelli, MP, Cho, BP. a, b-methylene-2’-deoxynucleoside 5’-triphosphates as noncleavable substrates for DNA polymerases: isolation, characterization, and stability studies of novel 2’-deoxycyclonucleosides, 3,5’-cyclo-dG, and 2,5’-cyclo-dT. J. Med. Chem., 6460-6470 (2008).
Liang, F, Cho, BP. Probing the thermodynamics of aminofluorene-induced translesion DNA synthesis by differential scanning calorimetry. J. Am. Chem. Soc., 12108-12109 (2007).
Meneni, S, Liang, F, Cho,BP. Examination of the long-range effects of aminofluorene-induced conformational heterogeneity and its relevance to the mechanisms of translesion DNA synthesis. J. Mol. Biol.,1387-1400 (2007).
American Association for Cancer Research (AACR)
American Chemical Society (ACS)
American Association for Colleges of Pharmacy (AACP)
International Society of Polycyclic Aromatic Compounds (ISPAC )
Rho Chi Society