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World J Biol Chem. Jul 26, 2011; 2(7): 173-176
Published online Jul 26, 2011. doi: 10.4331/wjbc.v2.i7.173
Detection of clustered DNA lesions: Biological and clinical applications
Alexandros Georgakilas
Alexandros Georgakilas, DNA Damage and Repair Laboratory, Department of Biology, Thomas Harriot College of Arts and Sciences, Howell Science Complex, East Carolina University, Greenville, NC 27858, United States
Author contributions: Georgakilas A solely contributed to this manuscript.
Supported by East Carolina University
Correspondence to: Alexandros Georgakilas, PhD, Associate Professor, DNA Damage and Repair Laboratory, Department of Biology, Thomas Harriot College of Arts and Sciences, Howell Science Complex, East Carolina University, Greenville, NC 27858, United States. georgakilasa@ecu.edu
Telephone: +1-252-3285446 Fax: +1-252-3284178
Received: March 30, 2011
Revised: May 7, 2011
Accepted: May 14, 2011
Published online: July 26, 2011
Abstract

Humans are daily exposed to background radiation and various sources of oxidative stress. My research has focused in the last 12 years on the effects of ionizing radiation on DNA, which is considered as the key target of radiation in the cell. Ionizing radiation and endogenous cellular oxidative stress can also induce closely spaced oxidatively induced DNA lesions called “clusters” of DNA damage or locally multiply damage sites, as first introduced by John Ward. I am now interested in the repair mechanisms of clustered DNA damage, which is considered as the most difficult for the cell to repair. A main part of my research is devoted to evaluating the role of clustered DNA damage in the promotion of carcinogenesis in vitro and in vivo. Currently in my laboratory, there are two main ongoing projects. (1) Study of the role of BRCA1 and DNA-dependent protein kinase catalytic subunit repair proteins in the processing of clustered DNA damage in human cancer cells. For this project, we use several tumor cell lines, such as breast cancer cell lines MCF-7 and HCC1937 (BRCA1 deficient) and human glioblastoma cells MO59J/K; and (2) Possible use of DNA damage clusters as novel cancer biomarkers for prognostic and therapeutic applications related to modulation of oxidative stress. In this project human tumor and mice tissues are being used.

Keywords: DNA damage clusters; DNA repair; Oxidative stress; Cancer; Biomarkers