The crystal structures of psoralen cross-linked DNAs: drug-dependent formation of Holliday junctions.

Eichman BF, Mooers BH, Alberti M, Hearst JE, Ho PS
J Mol Biol. 2001 308 (1): 15-26

PMID: 11302703 · DOI:10.1006/jmbi.2001.4567

The single-crystal structures are presented for two DNA sequences with the thymine bases covalently cross-linked across the complementary strands by 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT). The HMT-adduct of d(CCGCTAGCGG) forms a psoralen-induced Holliday junction, showing for the first time the effect of this important class of chemotheraputics on the structure of the recombination intermediate. In contrast, HMT-d(CCGGTACCGG) forms a sequence-dependent junction. In both structures, the DNA duplex is highly distorted at the thymine base linked to the six-member pyrone ring of the drug. The psoralen cross-link defines the intramolecular interactions of the drug-induced junction, while the sequence-dependent structure is nearly identical to the native Holliday junction of d(CCGGTACCGG) alone. The two structures contrast the effects of drug- and sequence-dependent interactions on the structure of a Holliday junction, suggesting a role for psoralen in the mechanism to initiate repair of psoralen-lesions in mammalian DNA.

Copyright 2001 Academic Press.

MeSH Terms (14)

Animals Base Pairing Base Sequence Cross-Linking Reagents Crystallography, X-Ray DNA DNA Adducts Ficusin Hydrogen Bonding Models, Molecular Nucleic Acid Conformation Recombination, Genetic Thymine Trioxsalen

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