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  • Sequence-Dependent Bending of DNA Induced by cisplatin:NMR structures of an A.T-Rich 14-mer duplex

    Author(s)
    Parkinson, JA
    Chen, Y
    Murdoch, PD
    Guo, ZJ
    Berners-Price, SJ
    Brown, T
    Sadler, PJ
    Griffith University Author(s)
    Berners-Price, Sue J.
    Year published
    2000
    Metadata
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    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°) 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°), leading to an overall helix bend of 52±9°. The platinum atom is displaced ...
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    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°) 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°), leading to an overall helix bend of 52±9°. The platinum atom is displaced from the planes of the coordinated G7* and G8* by 0.8 Å and 0.3 Å, 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°. 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.
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    Journal Title
    Chemistry: a European Journal
    Volume
    6,No 19
    DOI
    https://doi.org/10.1002/1521-3765(20001002)6:19<3636::AID-CHEM3636>3.0.CO;2-W
    Subject
    Chemical sciences
    History, heritage and archaeology
    Publication URI
    http://hdl.handle.net/10072/3210
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    • Journal articles

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