Structure of the DNA interstrand cross-link of 4,5',8-trimethylpsoralen

• Published in: Biochemistry (Easton) Vol. 31; no. 29; pp. 6774 - 6783
• Main Authors: KUMARESAN, K. R, MUTHUKUMAR RAMASWAMY, YEUNG, A. T
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 28-07-1992
• Subjects: Analytical, structural and metabolic biochemistry; Base Composition; Base Sequence; Biological and medical sciences; Cross-Linking Reagents - chemistry; DNA - chemistry; Dna, deoxyribonucleoproteins; Electrophoresis, Polyacrylamide Gel; Fundamental and applied biological sciences. Psychology; Hydrogen Bonding; Models, Structural; Molecular Sequence Data; Nucleic Acid Conformation; Nucleic acids; Oligodeoxyribonucleotides - chemical synthesis; Oligodeoxyribonucleotides - chemistry; Structure-Activity Relationship; Thymine; Trioxsalen - chemistry; Crosslink agent; Stability; Base pairing; DNA; Molecular adduct; Psoralen derivatives
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00144a018

4,5',8-Trimethylpsoralen (TMP) cross-links a 5' TpA or a 5' ApT site by photoreacting with one thymine moiety in each DNA strand. We are interested in whether psoralen interstrand cross-links all share one structure or whether there are significant differences. In this paper, we employed a rapid method for probing the structure of the cross-link by making a series of TMP cross-linked duplexes containing specific base-pair mismatches. The relative stability provided by a base pair can be correlated with neighboring base pairs by comparing the extents of gel retardation when base-pair mismatches happen in each position. From our studies, we infer that with respect to the furan-side strand, the 5'T.A base pair of the two T.A base pairs in the TpA site is not hydrogen bonded. Immediately on each side of the cross-linked TpA site is a highly stabilized base pair. Next, a region of decreased stability occurs in each arm of a cross-linked duplex and these base pairs of least stability are located farther away from the cross-linked thymines as the lengths of the arms of the cross-linked helix increase. Finally, even in 7 M urea at 49 degrees C the cross-linked helix is hydrogen bonded at both ends of a duplex of 22 base pairs. We propose that the structures of interstrand cross-links in DNA vary appreciably with the DNA sequence, the length of the DNA duplex, and the structures of the DNA cross-linking agents.