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

Wong H., Muftuoglu M. , Beck G., Imam S. Z. , Bohr V. A. , Wilson D. M.

NUCLEIC ACIDS RESEARCH, vol.35, no.12, pp.4103-4113, 2007 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 12
  • Publication Date: 2007
  • Doi Number: 10.1093/nar/gkm404
  • Title of Journal : NUCLEIC ACIDS RESEARCH
  • Page Numbers: pp.4103-4113


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 20-deoxyuridine, agents that introduce base excision repair (BER) DNA substrates/intermediates.