Regulation of WRN helicase activity in human base excision repair.

Abstract	Werner syndrome patients are deficient in the Werner protein (WRN), which is a multifunctional nuclear protein possessing 3'-5' exonuclease and ATP-dependent helicase activities. Studies of Werner syndrome cells and biochemical studies of WRN suggest that WRN plays a role in several DNA metabolic pathways. WRN interacts with DNA polymerase beta (pol beta) and stimulates pol beta strand displacement synthesis on a base excision repair (BER) intermediate in a helicase-dependent manner. In this report, we examined the effect of the major human apurinic/apyrimidinic endonuclease (APE1) and of pol beta on WRN helicase activity. The results show that WRN alone is able to unwind several single strand break BER intermediates. However, APE1 inhibits WRN helicase activity on these intermediates. This inhibition is likely due to the binding of APE1 to nicked apurinic/apyrimidinic sites, suggesting that APE1 prevents the promiscuous unwinding of BER intermediates. This inhibitory effect was relieved by the presence of pol beta. A model involving the pol beta-mediated hand-off of WRN protein is proposed based on these results.
Authors	Byungchan Ahn, Jeanine A Harrigan, Fred E Indig, David M Wilson 3rd, Vilhelm A Bohr
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 51 Pg. 53465-74 (Dec 17 2004) ISSN: 0021-9258 [Print] United States
PMID	15385537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Adenosine Triphosphate DNA Glutathione Transferase DNA Polymerase beta Exodeoxyribonucleases DNA Helicases RecQ Helicases WRN protein, human Werner Syndrome Helicase APEX1 protein, human DNA-(Apurinic or Apyrimidinic Site) Lyase
Topics	Adenosine Triphosphate (metabolism) DNA (metabolism) DNA Damage DNA Helicases (metabolism) DNA Polymerase beta (chemistry, metabolism) DNA Repair DNA-(Apurinic or Apyrimidinic Site) Lyase (metabolism) Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Exodeoxyribonucleases Gene Expression Regulation, Enzymologic Glutathione Transferase (metabolism) HeLa Cells Humans Immunoblotting Microscopy, Fluorescence Models, Genetic Mutation Nucleic Acid Denaturation Protein Binding RecQ Helicases Werner Syndrome (metabolism) Werner Syndrome Helicase

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