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DNA Distortion Caus...
DNA Distortion Caused by Uracil-Containing Intrastrand Cross-Links
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Churchill, C. D. M. (författare)
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- Eriksson, Leif A, 1964 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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Wetmore, S. D. (författare)
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(creator_code:org_t)
- 2016-02-15
- 2016
- Engelska.
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 120:7, s. 1195-1204
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Four uracil-containing intrastrand cross-links have been detected in human cells upon UV irradiation of 5-bromouracil-containing DNA, namely 5'-G[8-5]U-3', 5'-A[8-5]U-3', and 5'-A[2-5)U-3'. These lesions feature unique composition and connectivity compared with other intrastrand cross-links reported in the literature. For the first time, structural information obtained using molecular dynamics (MD) simulations reveal that all four lesions distort the DNA helix, which can involve an extrahelical location of the cross-link, changes in the helical interactions of the complementary nucleotides, or disruption of hydrogen bonding in the flanking base pairs up to two positions from the cross-linked site; however, the degree of distortion varies between the cross-links, being affected by the sequence, nucleobase-nucleobase connectivity, and the purine involved. Most importantly, the relative distortion of the damaged DNA provides the first structural explanation for the observed abundances of the four uracil-containing cross-links. Furthermore, the highly distorted conformations suggest that these lesions will likely have severe implications for DNA replication and repair processes in cells.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- bromodeoxyuridine-substituted dna
- molecular-dynamics simulations
- in-vitro replication
- double-strand breaks
- duplex dna
- guanine-thymine
- mammalian-cells
- force-field
- halogenated pyrimidines
- anaplastic
- astrocytoma
- Chemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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