Adenine versus guanine DNA adducts of aristolochic acids: role of the carcinogen-purine linkage in the differential global genomic repair propensity
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Date
2015
Authors
Kathuria, Preetleen
Sharma, Purshotam
Wetmore, Stacey D.
Journal Title
Journal ISSN
Volume Title
Publisher
Oxford University Press
Abstract
Computational modeling is employed to provide
a plausible structural explanation for the
experimentally-observed differential global genome
repair (GGR) propensity of the ALII-N2-dG and ALIIN6-
dA DNA adducts of aristolochic acid II. Our modeling
studies suggest that an intrinsic twist at the
carcinogen–purine linkage of ALII-N2-dG induces
lesion site structural perturbations and conformational
heterogeneity of damaged DNA. These structural
characteristics correlate with the relative repair
propensities of AA-adducts, where GGR recognition
occurs for ALII-N2-dG, but is evaded for intrinsically
planar ALII-N6-dA that minimally distorts DNA and
restricts the conformational flexibility of the damaged
duplex. The present analysis on the ALII adduct
model systems will inspire future experimental studies
on these adducts, and thereby may extend the
list of structural factors that directly correlate with
the propensity for GGR recognition.
Description
Sherpa Romeo green journal: open access
Keywords
Computational modeling , Aristolochic acids , Global genome repair , Carcinogen-purine linkage , DNA , DNA adducts
Citation
Kathuria, P., Sharma, P., & Wetmore, S. D. (2015). Adenine versus guanine DNA adducts of aristolochic acids: role of the carcinogen-purine linkage in the differential global genomic repair propensity. Nucleic Acids Research, (43(15), 7388-7397. doi:10.1093/narl/gkv701