DNA damage generated by the abstraction of any one of the five hydrogen atoms found at the sugar ring of a 2'-deoxyribonucleotide can yield a variety of lesions, some of which compromise cellular processes. Recently, the nature of DNA damage lesions resulting from the formation of a C3'-thymidinyl radical in DNA oligomers was found to be dependent on nucleic acid structure.  Architectures relevant to DNA replication were observed to generate larger amounts of strand breaks and 2'-deoxyxylothymidine lesions than the levels observed in duplex DNA (dsDNA), when experiments were conducted under aerobic conditions in the presence of a hydrogen atom donor. These results confirm previous studies that highlight the protective role of duplex DNA structure against oxidative damage processes.  To understand how this damage can affect the integrity of DNA, the impact of C3'-thymidinyl radical derived lesions on DNA stability and structure were characterized using biophysical methods.  Thermal melting and differential scanning calorimetric analysis were used to evaluate the biophysical properties of DNA architectures, including dsDNA, single 3' or 5'-overhangs (OvHgs), and pseudo-forks.  Each of the lesions created was found to have some effect on architecture stability.  Interestingly, the affect of the 2'-deoxyxylothymidine lesion is found to depend on DNA architecture and proximity to the 3' end of the damaged strand.

Oxidative DNA damage in replication relevant architectures

246th National Meeting (2013)

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