Adenine versus guanine DNA adducts of aristolochic acids: role of the carcinogen-purine linkage in the differential global genomic repair propensity

Thumbnail Image
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
Collections