OF WORK: We have defined the main mammalian base excision repair (BER) pathways in vitro using purified enzymes and cell extracts, and we have cloned the human and mouse genes for many of the enzymes, expressed the corresponding recombinant proteins in E. coli and insect cells, and prepared cell lines with genetic alterations in each gene. Transgenic mouse models are studied to understand the cellular and tissue requirements for each enzyme. This project includes studies of the cellular role of BER in overall cellular DNA repair, apoptosis, check point control of the cell cycle, mutagenesis, chromosome stability, DNA lesion bypass, cell signaling, DNA replication control, and human and mouse carcinogenesis.

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Horton, Julie K; Stefanick, Donna F; Prasad, Rajendra et al. (2014) Base excision repair defects invoke hypersensitivity to PARP inhibition. Mol Cancer Res 12:1128-39
Bienstock, Rachelle J; Beard, William A; Wilson, Samuel H (2014) Phylogenetic analysis and evolutionary origins of DNA polymerase X-family members. DNA Repair (Amst) 22:77-88
Masaoka, Aya; Gassman, Natalie R; Horton, Julie K et al. (2013) Interaction between DNA Polymerase * and BRCA1. PLoS One 8:e66801
Horton, Julie K; Stefanick, Donna F; Gassman, Natalie R et al. (2013) Preventing oxidation of cellular XRCC1 affects PARP-mediated DNA damage responses. DNA Repair (Amst) 12:774-85
Carrozza, Michael J; Stefanick, Donna F; Horton, Julie K et al. (2009) PARP inhibition during alkylation-induced genotoxic stress signals a cell cycle checkpoint response mediated by ATM. DNA Repair (Amst) 8:1264-72
Prasad, Rajendra; Longley, Matthew J; Sharief, Farida S et al. (2009) Human DNA polymerase theta possesses 5'-dRP lyase activity and functions in single-nucleotide base excision repair in vitro. Nucleic Acids Res 37:1868-77
Yoshizawa, Katsuhiko; Jelezcova, Elena; Brown, Ashley R et al. (2009) Gastrointestinal hyperplasia with altered expression of DNA polymerase beta. PLoS One 4:e6493
Kronenberg, Golo; Harms, Christoph; Sobol, Robert W et al. (2008) Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking uracil DNA glycosylase. J Neurosci 28:7219-30
Horton, Julie K; Watson, Mary; Stefanick, Donna F et al. (2008) XRCC1 and DNA polymerase beta in cellular protection against cytotoxic DNA single-strand breaks. Cell Res 18:48-63
Poltoratsky, Vladimir; Horton, Julie K; Prasad, Rajendra et al. (2008) Negligible impact of pol iota expression on the alkylation sensitivity of pol beta-deficient mouse fibroblast cells. DNA Repair (Amst) 7:830-3

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