Base excision repair and design of small molecule inhibitors of human DNA polymerase β

Cell Mol Life Sci. 2010 Nov;67(21):3633-47. doi: 10.1007/s00018-010-0489-1. Epub 2010 Sep 16.


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • DNA Polymerase beta / antagonists & inhibitors*
  • DNA Polymerase beta / chemistry
  • DNA Polymerase beta / metabolism*
  • DNA Repair / drug effects*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • High-Throughput Screening Assays
  • Humans
  • Models, Molecular


  • Enzyme Inhibitors
  • DNA Polymerase beta