title: Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an A.T-rich 14-mer duplex.
abstract: The NMR solution structure of the A.T rich DNA 14-mer duplex d(ATACATGGTACATA).d(TATGTACCATGTAT) is reported. This is compared with the NMR structure of the same duplex intrastrand cross-linked at the d(G*pG*) site by cis-(Pt(NH3)2¿2+, derived from the anticancer drug cisplatin. The unmodified duplex has B-DNA geometry, but there is a large positive base-pair roll (roll angle 24 +/- 2 degrees) at the T9-A10 step on the 3' side of the central GG site. Platination of the DNA duplex causes the adjacent guanine bases to roll toward one another (roll angle 44 +/- 4 degrees), leading to an overall helix bend of 52 +/- 9 degrees. The platinum atom is displaced from the planes of the coordinated G7* and G8* by 0.8 A and 0.3 A, respectively. The minor groove opposite the platinum lesion is widened and flattened, with geometric parameters similar to those of A-form DNA. The unwinding of the helix at the platination site is 26 degrees. Platination causes the DNA duplex to bend toward the 3'-end (with respect to the G*G* strand), in contrast to G C-rich structures reported previously, which bend toward the 5'-end. This difference can be attributed to the predisposition of the A.T rich duplex toward bending in this region. Protein recognition of bent platinated G*G* lesions may therefore exhibit a strong dependence on the local DNA structure.
authors.affiliation: Department of Chemistry, University of Edinburgh, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Parkinson
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: del Socorro Murdoch
authors.forename: Z
authors.initials: Z
authors.lastname: Guo
authors.forename: S J
authors.initials: SJ
authors.lastname: Berners-Price
authors.forename: T
authors.initials: T
authors.lastname: Brown
authors.forename: P J
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D001483:Base Sequence; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation
chemical_list: D004247:DNA; D002945:Cisplatin