Book of Abstracts: Albany 2007
June 19-23 2007
DNA Repeats, Unusual Structures and Genome Instability
Simple DNA repeats can adopt a plethora of non-B DNA conformations, including cruciforms, Z-DNA, three- and tetrastranded DNA structures, slip-stranded DNA etc. Over the last decade, my lab has demonstrated that formation of these structures during major genetic transactions, such as DNA replication and transcription, confuses those molecular machineries leading to genomic instability. This study concentrated on the effects of long inverted repeats in DNA replication. We have generated series of inverted repeats built of ALU retroposons, differing in the level of homology between the repetitive halves as well as the distance and base composition of the central spacer. The effect of these repeats on DNA replication in bacterial, yeast and mammalian cells was analyzed using 2-dimensional electrophoretic analysis of replication intermediates. It appeared that long inverted repeats block DNA replication in all these systems such that the strength of the blockage decreases near exponentially with an increase of sequence divergence between the repetitive halves. Our data implicate that formation of stable hairpins within the lagging strand template is responsible for the replication stalling. Processing of stalled replication is likely responsible for the chromosomal fragility and DNA rearrangements associated with long inverted repeats.
Sergei M. Mirkin
Department of Biology,