Analysis of non-B DNA structure at chromosomal sites in the mammalian genome.

Changes at sites of genetic instability ultimately involve DNA repair pathways. Some sites of genetic instability in the mammalian genome appear to be unstable because they adopt a non-B DNA conformation. We describe two structural approaches for determination of whether a genomic region is configured in a non-B DNA conformation. Our studies indicate that at least some chromosomal fragile sites can be explained by such altered DNA conformations. One of the methods that we describe is called the bisulfite modification assay. This is a powerful assay because it provides information on individual DNA molecules. The second approach uses preexisting DNA structural reagents, but describes our specific application of them to analysis of DNA in vivo.