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
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.