Cockayne syndrome B protein stimulates apurinic endonuclease 1 activity and protects against agents that introduce base excision repair intermediates

Nucleic Acids Res. 2007;35(12):4103-13. doi: 10.1093/nar/gkm404. Epub 2007 Jun 12.


The Cockayne syndrome B (CSB) protein--defective in a majority of patients suffering from the rare autosomal disorder CS--is a member of the SWI2/SNF2 family with roles in DNA repair and transcription. We demonstrate herein that purified recombinant CSB and the major human apurinic/apyrimidinic (AP) endonuclease, APE1, physically and functionally interact. CSB stimulates the AP site incision activity of APE1 on normal (i.e. fully paired) and bubble AP-DNA substrates, with the latter being more pronounced (up to 6-fold). This activation is ATP-independent, and specific for the human CSB and full-length APE1 protein, as no CSB-dependent stimulation was observed with Escherichia coli endonuclease IV or an N-terminal truncated APE1 fragment. CSB and APE1 were also found in a common protein complex in human cell extracts, and recombinant CSB, when added back to CSB-deficient whole cell extracts, resulted in increased total AP site incision capacity. Moreover, human fibroblasts defective in CSB were found to be hypersensitive to both methyl methanesulfonate (MMS) and 5-hydroxymethyl-2'-deoxyuridine, agents that introduce base excision repair (BER) DNA substrates/intermediates.

Publication types

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

MeSH terms

  • Cell Line, Transformed
  • DNA Helicases / metabolism*
  • DNA Helicases / physiology
  • DNA Repair Enzymes / metabolism*
  • DNA Repair Enzymes / physiology
  • DNA Repair*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism*
  • Genome, Human
  • Humans
  • Methyl Methanesulfonate / toxicity
  • Poly-ADP-Ribose Binding Proteins
  • Thymidine / analogs & derivatives
  • Thymidine / toxicity


  • Poly-ADP-Ribose Binding Proteins
  • 5-hydroxymethyl-2'-deoxyuridine
  • Methyl Methanesulfonate
  • DNA Helicases
  • ERCC6 protein, human
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • DNA Repair Enzymes
  • Thymidine