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Research Abstracts Online
January 2009 - March 2010

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University of Minnesota Twin Cities
Academic Health Center
Masonic Cancer Center

PI: Natalia Tretyakova
Co-PI: Darrin M. York, Fellow

Effects of Cytosine Analogs on DNA Adduct Formation

The reactivity of tobacco carcinogens towards guanines in DNA is affected by the presence of 5-methyl-cytosine (MeC) base paired to the reacting guanine. To further investigate this result, these researchers incorporated various 5-Me-C analogs into duplex oligonucleotides and determined the experimental reactivity data. Quantum mechanical calculations were then used to investigate the properties of these 5-substituted cytosines in order to rationalize the experimental results. The calculations were also used to identify other key cytosine analogs that could be used to probe the effect of 5-substituted cytosine on guanine reactivity with tobacco carcinogens. The researchers are performing further quantum mechanical and molecular dynamic calculations to investigate base pairing effects and DNA duplex structure and reactivity. Continued studies will analyze the effects of substitution at C-5 of dC on DNA duplex structure and possible attack conformations of different carcinogens.

Group Members

Thakshila Dissanayake Rallage, Visiting Researcher
George Giambasu, Graduate Student
Melissa M. Goggin, Graduate Student
Rebecca Guza, Graduate Student
Adam Moser, Graduate Student
Uthpala Seneviratne, Graduate Student