These sequences, which we call non-B sequences, include homopurine-homopyrimidine sequences that form intramolecular triplexes and a stretch of sequences that have an ATC sequence context that becomes continuously base unpaired, including neighboring sequences. The base-unpairing regions are typically found within matrix attachment regions (MARs) of genomic DNAs that have a high affinity to the nuclear matrix (1). Previously, we reported that intramolecular triplex structures form in vivo in response to negative supercoiling locally generated by the process of active transcription (2). Recently, we analyzed a new human fragile site on the human chromosome to examine if genome instability correlates with non-B DNA sequences. This is the site at which the SV40 integrate resides in a cluster of non-B DNA sequences. These unusual DNA characteristics may be intrinsic properties of common fragile sites (3). We are screening more fragile sites to establish this correlation. It is our goal to understand how non-B DNA structures trigger genome instability in mammalian cells.

We are also studying a series of single-stranded DNA and mRNA-binding proteins in mouse brain that are expressed in a developmental stage-specific manner. Some of them are capable of inducing the cell differentiation of PC12 cells into neuronal cells as evidenced by morphological changes (neurite outgrowth) and activation of a specific signaling pathway. We are currently identifying which mRNA are bound to these proteins in vivo and the biological consequence of such binding.