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The presence of 5',8-cyclo-2'-deoxyadenosine (5'S)-cdA induces modifications in the geometry of the DNA duplex in the 5'-end direction of the strand and in the 3'-end direction of the complementary strand. As a consequence, the enzymes are probably not able to adjust their active sites in this rigid structure. Additionally, clustered DNA damage sites, a signature of ionising radiation, pose a severe challenge to a cell's repair machinery, particularly base excision repair (BER). To date, clusters containing a DNA base lesion, (5'S)-cdA, which is repaired by nucleotide excision repair, have not been explored. We have therefore investigated whether bistranded clusters containing (5'S)-cdA influence the repairability of an opposed AP site lesion, which is repaired by BER. Using synthetic oligonucleotides containing a bistranded cluster with (5'S)-cdA and an AP site at different interlesion separations, we have shown that in the presence of (5'S)-cdA on the 5'-end side, repair of the AP site by the BER machinery is retarded when the AP site is ≤8 bases from the (5'S)-cdA. However, if (5'S)-cdA is located on the 3'-end side with respect to the AP site, the effect on its repair is much weaker and totally disappears for distances ≥8 bases.

Original publication

DOI

10.1039/c4ob01089b

Type

Journal article

Journal

Org Biomol Chem

Publication Date

21/11/2014

Volume

12

Pages

8671 - 8682

Keywords

Animals, Base Sequence, CHO Cells, Cell Nucleus, Cricetulus, DNA, DNA Damage, DNA Repair, Deoxyadenosines, Models, Molecular, Molecular Sequence Data, Oligonucleotides, Oxidation-Reduction, Quantum Theory, Thermodynamics, Uracil-DNA Glycosidase