PMID: 8943004Nov 26, 1996Paper

An unusual mechanism for the major human apurinic/apyrimidinic (AP) endonuclease involving 5' cleavage of DNA containing a benzene-derived exocyclic adduct in the absence of an AP site

Proceedings of the National Academy of Sciences of the United States of America
Bo HangB Singer

Abstract

The major human apurinic/apyrimidinic (AP) endonuclease (class II) is known to cleave DNA 5' adjacent to an AP site, which is probably the most common DNA damage produced hydrolytically or by glycosylase-mediated removal of modified bases. p-Benzoquinone (pBQ), one of the major benzene metabolites, reacts with DNA to form bulky exocyclic adducts. Herein we report that the human AP endonuclease directly catalyzes incision in a defined oligonucleotide containing 3,N4-benzetheno-2'-deoxycytidine (pBQ-dC) without prior generation of an AP site. The enzyme incises the oligonucleotide 5' to the adduct and generates 3'-hydroxyl and 5'-phosphoryl termini but leaves the pBQ-dC on the 5' terminus of the cleavage fragment. The AP function of the enzyme is not involved in this action, as no preexisting AP site is present nor is a DNA glycosylase activity involved. Nicking of the pBQ-dC adduct also leads to the same "dangling base" cleavage when two Escherichia coli enzymes, exonuclease III and endonuclease IV, are used. Our finding of this unusual mode of action used by both human and bacterial AP endonucleases raises important questions regarding the requirements for substrate recognition and catalytic active site(s) for this essential ce...Continue Reading

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Citations

Feb 9, 2006·Chemical Reviews·Patrick J O'Brien
Jun 5, 2010·Mutagenesis·Mark D EvansMarcus S Cooke
Aug 24, 2007·Nucleic Acids Research·Sophie Couvé-PrivatMurat K Saparbaev
Feb 26, 2009·Nucleic Acids Research·Lars SchomacherHans-Joachim Fritz
Sep 24, 2008·Molecular and Cellular Biology·Ranajoy ChattopadhyayKishor K Bhakat
Aug 10, 2007·Molekuliarnaia biologiia·N S DyrkheevaO I Lavrik
Jan 15, 2011·Journal of Nucleic Acids·Bo Hang
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·B HangB Singer
Jan 6, 2004·Nucleic Acids Research·Laurent GrosMurat K Saparbaev
Feb 3, 2007·Chemico-biological Interactions·Bo Hang, Anton B Guliaev
Sep 27, 2005·DNA Repair·Zhongwen XieZhigang Wang
Jan 24, 2002·Nature·Alexander A Ischenko, Murat K Saparbaev
Oct 23, 2004·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Bo Hang
Nov 7, 1998·The Journal of Biological Chemistry·Y MasudaB Demple
Feb 1, 2013·EcoSal Plus·Sophie CouvéMurat Saparbaev
Feb 19, 2002·Chemical Reviews·Sheila S. David, Scott D. Williams

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