Graduate Program Information
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Professor of Biochemistry and Biophysics
Ph.D. Pennsylvania State University 1968

The use of radiation-related technologies in medical diagnostics, industrial applications, power generation, and national defense continues to grow. In each application it is necessary to weigh benefits against risk. Quantifying risk is particularly difficult in cases where radiation exposures are at a low dose rate for a long time period. Consequences of such low dose exposures are radiation-induced cancer and leukemia. In order to solve this difficult problem, radiation produced alterations in the biochemical machinery must be identified. Particularly important is the type and frequency of damage inflicted on DNA.

The aim of our research program is to fully characterize the free radical processes by which ionizing radiation, through direct effects, alters the chemical structure of DNA. The ultimate goal is to develop a set of rules that will predict the chemical damage that results when DNA is exposed to ionizing radiation.

Our approach is to use electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) to study free radical processes initiated in DNA by ionizing radiation. Oligodeoxynucleotides of known sequence and predetermined crystal structure are used to investigate how the base sequence and local environment influence the distribution of electrons and holes trapped on DNA. The distribution, which effectively means the type and yield of trapped free radicals, is fundamental to understanding electron transfer, rearrangement, and radical combination reactions in DNA. The free radical reactions, ultimately terminate in stable diamagnetic damage. Using a variety of analytical tools, e.g., HPLC and NMR, stable end products are correlated with free radical precursors. Thus, we are able to discover the mechanisms by which initial ionization result in specific types of DNA damage, the damage that confronts the cells repair enzymes.

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Recent Publications

Purkayastha S, Milligan JR, Bernhard WA (2008) An investigation into the mechanisms of DNA strand breakage by direct ionization of variably hydrated plasmid DNA. J Phys Chem B, 112:4152

Swarts SG, Gilbert DC, Sharma KK, Razskazovskiy Y, Purkayastha S, Naumenko KA, Bernhard WA (2007) Mechanisms of direct radiation damage in DNA, based on a study of the yields of base damage, deoxyribose damage, and trapped radicals in d(GCACGCGTGC)(2). Radiat Res, 168:367-81

Purkayastha S, Milligan JR, Bernhard WA (2007) On the chemical yield of base lesions, strand breaks, and clustered damage generated in plasmid DNA by the direct effect of X rays. Radiat Res, 168:357-66

Sharma KK, Purkayastha S, Bernhard WA (2007) Unaltered free base release from d(CGCGCG)2 produced by the direct effect of ionizing radiation at 4 K and room temperature. Radiat Res, 167:501-7

Roginskaya M, Bernhard WA, Razskazovskiy Y (2006) Protection of DNA against direct radiation damage by complex formation with positively charged polypeptides. Radiat Res, 166:9-18

Purkayastha S, Milligan JR, Bernhard WA (2006) The role of hydration in the distribution of free radical trapping in directly ionized DNA. Radiat Res, 166:1-8

Purkayastha S, Milligan JR, Bernhard WA (2006) An investigation into the mechanisms of DNA strand breakage by direct ionization of variably hydrated plasmid DNA. J Phys Chem B Condens Matter Mater Surf Interfaces Biophys, 110:26286-91

Purkayastha S, Milligan JR, Bernhard WA (2005) Correlation of free radical yields with strand break yields produced in plasmid DNA by the direct effect of ionizing radiation. J Phys Chem B Condens Matter Mater Surf Interfaces Biophys, 109:16967-73

Roginskaya M, Razskazovskiy Y, Bernhard WA (2005) 2-Deoxyribonolactone lesions in X-ray-irradiated DNA: quantitative determination by catalytic 5-methylene-2-furanone release. Angew Chem Int Ed Engl, 44:6210-3

Roginskaya M, Bernhard WA, Marion RT, Razskazovskiy Y (2005) The release of 5-methylene-2-furanone from irradiated DNA catalyzed by cationic polyamines and divalent metal cations. Radiat Res, 163:85-9

Roginskaya M, Bernhard WA, Razskazovskiy Y (2004) Diffusion approach to long distance charge migration in DNA: time-dependent and steady-state analytical solutions for the product yields. J Phys Chem B, 108:2432-2437

Purkayastha S, Bernhard WA (2004) What is the Initial Chemical Precursor of DNA Strand Breaks Generated by Direct-type Effects?. J Phys Chem B, 108:18377-18382

Bernhard WA, Close DM (2004) DNA damage dictates the biological consequences of ionizing irradiation: the chemical pathways. In: Charged Particle and Photon Interactions with Matter. (Y. Hatano and A. Mozumder), pp. 431-470

Razskazovskiy Y, Debije MG, Howerton SB, Williams LD, Bernhard WA (2003) Strand breaks in X-irradiated crystalline DNA: alternating CG oligomers. Radiat Res, 160:334-9

Razskazovskiy Y, Debije MG, Bernhard WA (2003) Strand breaks produced in X-irradiated crystalline DNA: influence of base sequence. Radiat Res, 159:663-9

Debije MG, Close DM, Bernhard WA (2002) Reductive damage in directly ionized DNA: saturation of the C5=C6 bond of cytosine in d(CGCG)(2) crystals. Radiat Res, 157:235-42

Debije MG, Bernhard WA (2002) Thermally stable sites for electron capture in directly ionized DNA: free radicals produced by the net gain of hydrogen a C5/C6 of cytosine and thymine in crystalline oligodeoxynucleotides. J. Phys. Chem. A, 106:4608-4615

Graduate students in my laboratory work toward a Ph.D. degree in the following program[s]:

Ph.D. in Biophysics

Ph.D. candidates in my laboratory may also be affiliated with these programs:

Contact Information

E-Mail: william_bernhard@urmc.rochester.edu

William Bernhard
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642

Office: Medical Center B-6835
Telephone: (585) 275-3730; Fax: (585) 275-6007