DNA base excision repair: a mechanism of trinucleotide repeat expansion

Trends Biochem Sci. 2012 Apr;37(4):162-72. doi: 10.1016/j.tibs.2011.12.002. Epub 2012 Jan 27.


The expansion of trinucleotide repeat (TNR) sequences in human DNA is considered to be a key factor in the pathogenesis of more than 40 neurodegenerative diseases. TNR expansion occurs during DNA replication and also, as suggested by recent studies, during the repair of DNA lesions produced by oxidative stress. In particular, the oxidized guanine base 8-oxoguanine within sequences containing CAG repeats may induce formation of pro-expansion intermediates through strand slippage during DNA base excision repair (BER). In this article, we describe how oxidized DNA lesions are repaired by BER and discuss the importance of the coordinated activities of the key repair enzymes, such as DNA polymerase β, flap endonuclease 1 (FEN1) and DNA ligase, in preventing strand slippage and TNR expansion.

Publication types

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

MeSH terms

  • Animals
  • DNA Polymerase beta / genetics
  • DNA Polymerase beta / metabolism
  • DNA Repair / genetics*
  • DNA Repair / physiology*
  • Flap Endonucleases / genetics
  • Flap Endonucleases / metabolism
  • Humans
  • Models, Biological
  • Trinucleotide Repeat Expansion / genetics*
  • Trinucleotide Repeat Expansion / physiology*


  • DNA Polymerase beta
  • Flap Endonucleases