Dr. McCullough received her doctoral degree in Cellular and Molecular Biology from the University of Vermont. She completed postdoctoral training at Oregon Health & Science University and the University of Texas Medical Branch in Galveston Texas. She was an Assistant Professor in the Department of Human Biological Chemistry and Genetics at the University of Texas before joining CROET in August 2003.

Research interests in the McCullough laboratory are focused on the biochemical mechanisms of DNA base excision repair systems and the regulation and roles of DNA repair in cellular responses to environmental stress. Ultimately, we are interested in correlating alterations in these systems with human cancers, aging, and other disease states. Currently our research is focused primarily on two distinct DNA repair processes: 1) mechanisms and regulation of human oxidative DNA damage-specific repair and 2) biochemical mechanisms and therapeutic applications of ultraviolet (UV) light-induced DNA damage-specific glycosylases. In the area of oxidative DNA damage and repair, we primarily focus on the human MutY (hMYH) enzyme that functions as an adenine-specific DNA glycosylase. This enzyme is crucial in mutation avoidance following replication of DNAs containing 8-oxoguanine, where polymerases tend to incorporate adenine opposite the oxidized guanine. Failure to remove the adenine results in GC to TA transversion mutations. Ongoing projects in this area in the lab are investigating the following:

• Biochemical and cellular characterization of mutants of hMYH that are associated with colorectal tumors and hepatocellular carcinomas.
• Replication-coupling of the repair of adenine:8-oxoguanine mispairs.
• Functional significance of human polymorphic variants in hMYH.
• Subcellular targeting of hMYH.

In the area of ultraviolet light-induced DNA damage and repair we are currently investigating the following:

• Biochemical and structural basis for the glycosylase/lyase enzymes interactions with DNA.
• The role of base flipping in specific DNA-enzyme interactions and catalysis.
• The use of virally-encoded UV-specific glycosylases to engineer more efficient enzymes with potential therapeutic use in preventing UV-induced non-melanoma skin cancers and immunosuppression.

Wooden, S. H., Bassett, H. M., Wood, T.G., and McCullough, A.K. Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer. Cancer Letters (in press).

Jaruga, P., Jabil, R., McCullough, A.K., Rodriguez, H., Dizdaroglu, M., and Lloyd, R.S. Chlorella virus pyrimidine dimer glycosylase excises ultraviolet radiation- and hydroxyl radical-induced products 4,6-diamino-5-formamidopyrimidine and 2,6-diamino-4-hydroxy-5-formamidopyrimidine from DNA. Photochemistry and Photobiology 75(2):85-91, 2002.

Boldogh, I., Milligan, D., Lee, M.S., Bassett, H., Lloyd, R.S. and McCullough, A.K. hMYH cell cycle-dependent expression, subcellular localization and association with replication foci: evidence suggesting replication-coupled repair of adenine:8-oxoguanine mispairs. Nucleic Acids Research 29:2802-2809, 2001.

McCullough, A.K., Sanchez, A., Dodson, M.L., Marapaka, P. Taylor, J-S, and Lloyd, R.S. The Reaction Mechanism of DNA Glycosylase/AP Lyases at Abasic Sites. Biochemistry 40: 561-568, 2001.

Sun. L., McCullough, A.K., Lloyd, R.S., Wood, T.G., Adams, B., Grunon, J., Li, Y., and Van Etten, J. L. Intron conservation in a UV-specific DNA repair gene. J. Molecular Evolution 50: 82-92, 2000.

Piersen, C., McCullough, A. K. and Lloyd, R.S. AP lyases and dRPases: Commonality of mechanism. Mutation Research 459(1): 43-53, 2000.

McCullough, A. K., Dodson, M. L., and Lloyd, R. S. Initiation of base excision repair: Glycosylase mechanisms and structures. Annual Review of Biochemistry, vol. 68: 255-285; 1999.

McCullough, A. K., Romberg, M. T, Nyaga, S., Wei, Y., Wood, T. G.,Taylor, J-S., Van Etten, J. L., Dodson, M. L., and Lloyd, R.S. Characterization of a novel cis-syn and trans-syn II pyrimidine dimer glycosylase/AP lyase from a eukaryotic algal virus, Paramecium bursaria chlorella Virus-1. J. Biol. Chem. 273: 13136-13142, 1998.

McCullough, A. K., Dodson, M. L., Scharer, O. D., and Lloyd, R.S. The role of base flipping in damage recognition and catalysis by T4 Endonuclease V. J. Biol. Chem. 272: 27210-27217, 1997.