title: Base excision repair and design of small molecule inhibitors of human DNA polymerase β.
abstract: Base excision repair (BER) can protect a cell after endogenous or exogenous genotoxic stress, and a deficiency in BER can render a cell hypersensitive to stress-induced apoptotic and necrotic cell death, mutagenesis, and chromosomal rearrangements. However, understanding of the mammalian BER system is not yet complete as it is extraordinarily complex and has many back-up processes that complement a deficiency in any one step. Due of this lack of information, we are unable to make accurate predictions on therapeutic approaches targeting BER. A deeper understanding of BER will eventually allow us to conduct more meaningful clinical interventions. In this review, we will cover historical and recent information on mammalian BER and DNA polymerase β and discuss approaches toward development and use of small molecule inhibitors to manipulate BER. With apologies to others, we will emphasize results obtained in our laboratory and those of our collaborators.
authors.affiliation: Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA. wilson5@niehs.nih.gov
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Wilson
authors.forename: William A
authors.initials: WA
authors.lastname: Beard
authors.forename: David D
authors.initials: DD
authors.lastname: Shock
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Batra
authors.forename: Nisha A
authors.initials: NA
authors.lastname: Cavanaugh
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
authors.forename: Esther W
authors.initials: EW
authors.lastname: Hou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Asagoshi
authors.forename: Julie K
authors.initials: JK
authors.lastname: Horton
authors.forename: Donna F
authors.initials: DF
authors.lastname: Stefanick
authors.forename: Padmini S
authors.initials: PS
authors.lastname: Kedar
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Carrozza
authors.forename: Aya
authors.initials: A
authors.lastname: Masaoka
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Heacock
mesh_terms: D000818:Animals; D019951:DNA Polymerase beta / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D006801:Humans; D008958:Models, Molecular
chemical_list: D004791:Enzyme Inhibitors; D019951:DNA Polymerase beta