SUNY at Albany
June 19-23, 2001
Crystal structures of DNA Holliday junctions: Effects of sequence, ions, and drugs.
DNA recombination was first recognized as a means to introduce genetic diversity in cells. More recently, the mechanism of recombination has become implicated as an important cellular mechanism to repair or replicate through DNA lesions, and hyperactive recombination has been associated with BloomÕs Syndrome. All of these processes undergo a mechanism analogous to that proposed by Holliday in 1964 for homologous recombination, and involve a four-stranded intermediate in which DNA strands cross-over between two homologous duplexes to effect an exchange of genetic material. The structure of the four-way holliday junction has only recently been solved by single crystal X-ray diffraction. A comparison of the 2.1-2.2 ? resolution structures of d(CCGGGACCGG) and d(CCGGTACCGG) defines the sequence and the common intramolecular interactions that help to stabilize Holliday junctions. In addition, the structures of the psoralen cross-linked sequences d(CCGGTACCGG) and d(CCGCTAGCGG) contrast the effects of this chemotheraputic agent on a sequence stabilized versus a drug-induced junction. Finally, the high resolution (1.5 ?) structure of d(CCGGTACm5CGG) reveals how cytosine methylation affects the overall structure, the intramolecular interactions, and the distribution of cations around the Holliday junction.
P. Shing Ho, Brandt F. Eichman, and Jeffrey M. Vargason,
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.