Biology of Mammalian Base Excision Repair

Wilson, Samuel H.

Abstract

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.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Environmental Health Sciences (NIEHS)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAES050159-13
• Application #: 7968069
• Support Year: 13
• Fiscal Year: 2009
• Total Cost: $2,337,161

Institution

• Name: National Institute of Environmental Health Sciences

Publications

Gassman, Natalie R; Coskun, Erdem; Jaruga, Pawel et al. (2016) Combined Effects of High-Dose Bisphenol A and Oxidizing Agent (KBrO3) on Cellular Microenvironment, Gene Expression, and Chromatin Structure of Ku70-deficient Mouse Embryonic Fibroblasts. Environ Health Perspect 124:1241-52

Prasad, Rajendra; Dyrkheeva, Nadezhda; Williams, Jason et al. (2015) Mammalian Base Excision Repair: Functional Partnership between PARP-1 and APE1 in AP-Site Repair. PLoS One 10:e0124269

Ça?layan, Melike; Horton, Julie K; Prasad, Rajendra et al. (2015) Complementation of aprataxin deficiency by base excision repair enzymes. Nucleic Acids Res 43:2271-81

Ça?layan, Melike; Horton, Julie K; Wilson, Samuel H (2015) Enzymatic Activity Assays for Base Excision Repair Enzymes in Cell Extracts from Vertebrate Cells. Bio Protoc 5:

Gassman, Natalie R; Coskun, Erdem; Stefanick, Donna F et al. (2015) Bisphenol a promotes cell survival following oxidative DNA damage in mouse fibroblasts. PLoS One 10:e0118819

Fedeles, Bogdan I; Freudenthal, Bret D; Yau, Emily et al. (2015) Intrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer. Proc Natl Acad Sci U S A 112:E4571-80

Ça?layan, Melike; Wilson, Samuel H (2015) Oxidant and environmental toxicant-induced effects compromise DNA ligation during base excision DNA repair. DNA Repair (Amst) 35:85-9

Gassman, Natalie R; Wilson, Samuel H (2015) Micro-irradiation tools to visualize base excision repair and single-strand break repair. DNA Repair (Amst) 31:52-63

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

Wilson, Samuel H (2014) The dark side of DNA repair. Elife 3:e03068