DNA structural reorganization upon conversion of a psoralen furan-side monoadduct to an interstrand cross-link: implications for DNA repair.

TitleDNA structural reorganization upon conversion of a psoralen furan-side monoadduct to an interstrand cross-link: implications for DNA repair.
Publication TypeJournal Article
Year of Publication1995
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue6
Pagination2345-9
Date Published1995 Mar 14
ISSN0027-8424
AbstractWe have used 1H NMR spectroscopy to determine the structural changes induced in the DNA oligomer d(5'-GCGTACGC-3')2 upon conversion of the 4'-hydroxy-methyl-4,5',8-trimethylpsoralen-DNA furan-side monoadduct (MAf) to the interstrand cross-link (XL). The MAf is a photochemical intermediate on the path to interstrand XL and has the psoralen intercalated into the helix. The local DNA structure is distorted in both adducts, but it returns to normal within three base pairs. The formation of XL requires displacement of the psoralen toward the initially unmodified strand, accompanied by a change in the hybridization of the thymine C-5 and C-6 carbons and a change in the local helix twist. The MAf is intercalated in the helix. There is no significant bend in the helix axis of either the MAf or XL. There are significant changes in the local helix dynamics upon photoadduct formation that may be recognized by cellular DNA repair enzyme systems. We hypothesize that the repair enzymes target lesions by detecting the conformational flexibility of the sugar-phosphate backbone induced by DNA-damaging agents.
URLhttp://www.pnas.org/cgi/pmidlookup?view=long&pmid=7892269
PubMed Linkhttp://www.ncbi.nlm.nih.gov/pubmed/7892269?dopt=Abstract
Short TitleProc Natl Acad Sci U S A