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PMID: 17567611 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

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

Nucleic acids research ·Vol. 35 ·No. 12 ·2007-00-00 ·Pages 4103-13

Wong HK, Muftuoglu M, Beck G, Imam SZ, Bohr VA, Wilson DM

Abstract

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.

MeSH Terms
Cell Line, Transformed DNA Helicases/metabolism,physiology DNA Repair DNA Repair Enzymes/metabolism,physiology DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism Genome, Human Humans Methyl Methanesulfonate/toxicity Poly-ADP-Ribose Binding Proteins Thymidine/analogs & derivatives,toxicity
Chemicals
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
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wong Heng-Kuan
Laboratory of Molecular Gerontology, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Muftuoglu Meltem
Beck Gad
Imam Syed Z
Bohr Vilhelm A
Wilson David M
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkm404
Published
2007-00-00
Epub
2007-00-12
Pages
4103-13
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1919475
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1093/nar/gkm404 PMC Full Text View journal details
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