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Susan P. LeDoux,
Ph.D.
Professor and Vice-Chair Postdoctoral Studies: University of South Alabama Ph.D. – University of South Alabama |
Cells of the human body are continuously exposed to agents which damage their DNA and lead to genetic alterations. As part of the normal homeostatic mechanisms of the cell, there are a group of proteins which are collectively referred to as DNA repair enzymes. These enzymes survey the DNA, recognize abnormalities, remove them and return the DNA to its normal sequence and configuration. Any decrease in the capacity or efficiency of these repair mechanisms can lead to an increase in genetic instability which is a hallmark characteristic of diseases such as cancer. The major areas of interest in this laboratory involve the role that DNA repair of environmentally induced damage plays in diseases of the central nervous system.
Initially, DNA repair studies assessed repair across the entire genome. However, as our knowledge of gene structure improved concomitantly with the introduction of new technologies, it has become apparent that DNA repair of many types of lesions is not homogenous across the entire genome. Therefore, this laboratory investigates DNA repair using techniques to quantitatively measure the formation and removal of DNA lesions across the entire genome, within specific nuclear and mitochondrial sequences, and by using ligation_mediated PCR at the level of individual nucleotides.
Representative Publications:
Druzhyna, NM, Hollensworth, SB, Kelley, MR, Wilson, GL, and Ledoux, SP. Targeting human 8-oxoguanine glysosylase to mitochondria of oligodendrocytes protects against menadione-induced oxidative stress. Glia 42:370-378 (2003).
- Bozner, P, Druzhyna, NM, Bryant-Thomas, TK, LeDoux, SP, Wilson, GL, and Pappolla, MA. Deficiency of chaperonin 60 in Down's syndrome. J Alzheimer's Dis. 4:479-486 (2002).
Shokolenko, IN, Alexeyev, MF, Robertson, FM, LeDoux, SP, and Wilson, GL. The expression of Exonuclease III from E. coli in mitochondria of breast cancer cells diminishes mitochondrial repair capacity and cell survival after oxidative stress. DNA Repair (Amst.) 2:471-482 (2003).
- Dobson, AW, Grishko, V, LeDoux, SP, Kelley, MR, Wilson, GL, and Gillespie, MN. Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death. Am J Physiol Lung Cell Mol Physiol. 283:L205-210 (2002).
Dobson, AW, Kelley MR, Wilson, GL, and LeDoux, SP. Targeting DNA repair proteins to mitochondria. Methods Mol Biol. 197:351-362 (2002).
Rachek, LI, Oberyszn, TM, D'Ambrosio, SM, Saavedra, JE, Keefer, LK, LeDoux, and Wilson, GL. Conditional targeting of the DNA repair enzyme hOGG1 into mitchondria. J Biol Chem. 277:44932-44937 (2002).
Shokolenko, I, Oberyszyn, T.M., D’Ambrosio, S.M., Saavedra, J.E., Keefer, L.K., LeDoux, S.P., Wilson, G.L., and Robertson, F.M. Protection of human keratinocyte mtDNA by low-level nitric oxide. Nitric Oxide 5:555-60 (2001).
Grishko, V., Solomon, M., Breit, J.F., Killilea, D.W., LeDoux, S.P., Wilson, G.L., and Gillespie, M.N. Hypoxia promotes oxidative base modifications in the pulmonary artery endothelial cell VEGF gene. FASEB Journal 15:1267-1269 (2001).
Grishko, V., Solomon, M., Wilson, G.L., LeDoux, S.P., and Gillespie, M.N. Oxygen radical-induced mitochondrial DNA damage and repair in pulmonary vascular endothelial cell phenotypes. Am J Physiol. Lung Cell Mol Physiol. 280:L1300-L1308 (2001).
Wang, G., Chen, Z., Zhang, S., Wilson, G.L., and Jing, K. Detection and determination of oligonucleotide triplex formation-mediated transcription-coupled DNA repair in HeLa nuclear extracts. Nucleic Acids Res. 29:1801-1807 (2001).
Dobson, A.W., Xu, Y., LeDoux, S.P., and Wilson, G.L. Enhanced mtDNA repair and cellular survival following oxidative stress by targeting the hOGG repair enzyme to mitochondria. J Biol Chem. 275:37518-37523 (2000).
Dobson, A.W., Xu, Y., Kelley, M.R., LeDoux, S.P., and Wilson, G. L. Enhanced mtDNA Repair and Cellular Survival Following Oxidative Stress by Targeting the hOGG Repair Enzyme to Mitochondria. J. Biol. Chem.275: 37518-37523 (2000).
Hollensworth, B.S., Shen,C., Sim,J.E., Spitz,D.R., Wilson,G.L., and LeDoux, S.P. Glial Cell Type-Specific Responses to Menadione-Induced Oxidative Stress. Free Radical Biology and Medicine 28:1161-1174 (2000).
Druzhyna. N., Smulson, M. E. LeDoux, S. P., and Wilson, G.L. Poly (ADP-Ribose) Polymerase Facilitates the Repair of N-Methylpurines in Mitochondrial DNA. Diabetes 49: 1849-1855 (2000)
Grishko, V. I., Druzhyna, N., LeDoux, S. P., and Wilson, G. L. Nitric Oxide-induced Damage to mtDNA and its Subsequent Repair, Nucleic Acids Research 27:4510-4515 (1999).
LeDoux, S.P., Driggers, W.J., Hollensworth, B.S., and Wilson, G.L. Repair of Alkylation and Oxidative Damage in Mitochondrial DNA. Mutation Research 434:149-159 (1999).