The crystal structures of psoralen cross-linked DNAs: drug-dependent formation of Holliday junctions.
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.
Eichman
B F
BF
Department of Biochemistry and Biophysics, ALS 2011, Oregon State University, Corvallis, OR 97331, USA.
Mooers
B H
BH
Alberti
M
M
Hearst
J E
JE
Ho
P S
PS
D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D003432:Cross-Linking Reagents / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005363:Ficusin / Q000378:metabolism*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011995:Recombination, Genetic / Q000235:genetics*; D013941:Thymine / Q000737:chemistry / Q000378:metabolism; D014307:Trioxsalen / Q000031:analogs & derivatives / Q000378:metabolism
D003432:Cross-Linking Reagents; D018736:DNA Adducts; C016507:hydroxymethyltrioxsalen; D004247:DNA; D005363:Ficusin; D013941:Thymine; D014307:Trioxsalen