The 5′-GNC site for DNA interstrand cross-linking is conserved for diepoxybutane stereoisomers

Julie T. Millard, Trevor C. Hanly, Kris Murphy, Natalia Tretyakova

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The bifunctional alkylating agent 1,2,3,4-diepoxybutane forms interstrand DNA-DNA cross-links between the N7 positions of deoxyguanosine residues on opposite strands of the duplex. For racemic diepoxybutane, these cross-links predominate within 5′-GNC/3′CNG sequences, where N is any nucleotide. We used denaturing polyacrylamide gel electrophoresis (dPAGE) to examine the role of stereochemistry in the cross-linking reaction, subjecting a restriction fragment to cross-linking with S,S-DEB, R,R-DEB, or meso-DEB. DNA cross-links generated by each isomer were isolated by dPAGE, and the sites of cross-linking were identified by sequencing gel analysis of DNA fragments generated by hot piperidine cleavage. We found that the 5′-GNC consensus sequence of racemic DEB is conserved, but the efficiencies of cross-linking vary, with S,S- > R,R- > meso-DEB. These results help explain the observed differences between the biological activities of DEB stereoisomers.

Original languageEnglish (US)
Pages (from-to)16-19
Number of pages4
JournalChemical research in toxicology
Volume19
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint Dive into the research topics of 'The 5′-GNC site for DNA interstrand cross-linking is conserved for diepoxybutane stereoisomers'. Together they form a unique fingerprint.

Cite this