Destruction of quadruplex by proteins, and its biological implications in replication and telomere maintenance

The minisatellite DNA Pc-1 consists of tandem re-peats of d(GGCAG). We previously reported that a d (GGCAG), strand folds into an intramolecular quadruplex under physiological conditions and that during replication the progression of DNA poly-merase is blocked by the quadruplex in vitro. There-fore, the formation of the quadruplex was supposed to be responsible for the hypermutable features of Pc-1. Then, we have identified proteins that bind to Pc-1, one of which is hnRNP Al. Here, we have demon-strated that hnRNP A1 destroys the quadruplex of Pc-1 on binding and abrogates the arrest of DNA po-lymerase at the repeat. Thus, hnRNP A1 functions as if it is a chaperon to assist Pc-1 DNA to form the proper folding suitable for replication. We have also found that hnRNP A1 and a related protein, hnRNP D, destroy the quadruplex of telomere DNA, which suggests the involvement of these proteins in telomere maintenance as DNA chaperons