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Structural Impact of Single Ribonucleotide Residues in DNA
Author(s) -
Evich Marina,
SpringConnell Alexander M.,
Storici Francesca,
Germann Markus W.
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600385
Subject(s) - ribonucleotide , phosphodiester bond , deoxyribose , dna , stereochemistry , ribose , nucleotide , chemistry , deoxyribonucleotide , base pair , pyrimidine , purine , dna replication , duplex (building) , biochemistry , crystallography , oligonucleotide , enzyme , rna , gene
Single ribonucleotide intrusions represent the most common nonstandard nucleotide type found incorporated in genomic DNA, yet little is known of their structural impact. This lesion incurs genomic instability in addition to affecting the physical properties of the DNA. To probe for structural and dynamic effects of single ribonucleotides in various sequence contexts—AxC, CxG, and GxC, where x=rG or dG—we report the structures of three single‐ribonucleotide‐containing DNA duplexes and the corresponding DNA controls. The lesion subtly and locally perturbs the structure asymmetrically on the 3′ side of the lesion in both the riboguanosine‐containing and the complementary strand of the duplex. The perturbations are mainly restricted to the sugar and phosphodiester backbone. The ribose and 3′‐downstream deoxyribose units are predominately in N‐type conformation; backbone torsion angles ϵ and/or ζ of the ribonucleotide or upstream deoxyribonucleotide are affected. Depending on the flanking sequences, the C2′−OH group forms hydrogen bonds with the backbone, 3′‐neighboring base, and/or sugar. Interestingly, even in similar purine‐rG‐pyrimidine environments (A‐rG‐C and G‐rG‐C), a riboguanosine unit affects DNA in a distinct manner and manifests different hydrogen bonds, which makes generalizations difficult.