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

Citation
Bf. Eichman et al., The crystal structures of psoralen cross-linked DNAs: Drug-dependent formation of Holliday junctions, J MOL BIOL, 308(1), 2001, pp. 15-26
Citations number
58
Categorie Soggetti
Molecular Biology & Genetics
Journal title
JOURNAL OF MOLECULAR BIOLOGY
ISSN journal
00222836 → ACNP
Volume
308
Issue
1
Year of publication
2001
Pages
15 - 26
Database
ISI
SICI code
0022-2836(20010420)308:1<15:TCSOPC>2.0.ZU;2-V
Abstract
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(CCG CTAGCGG) forms a psoralen-induced Holliday junction, showing for the first time the effect of this important class of chemotheraputics on the structur e of the recombination intermediate. In contrast, HMT-d(CCGGTACCGG) forms a sequence-dependent junction. Ln both structures, the DNA duplex is highly distorted at the thymine base linked to the six-member pyrone ring of the d rug. The psoralen cross-link defines the intramolecular interactions of the drug-induced junction, while the sequence-dependent structure is nearly id entical to the native Holliday junction of d(CCGGTACCGG) alone. The two str uctures contrast the effects of drug- and sequence-dependent interactions o n the structure of a Holliday junction, suggesting a role for psoralen in t he mechanism to initiate repair of psoralen-lesions in mammalian DNA. (C) 2 001 Academic Press.