Translocation of unstable heterochromatin as the mechanism of sister chromatid exchange formation: a proposed hypothesis.

The phenomenon of sister chromatid exchange has remained an enigma in that the actual mechanism for its formation has never been elucidated. It has long been suspected that the process involves some form of breakage and rejoining of DNA, but that hypothesis has never been proved. Recent work in this laboratory using cells from a premature aging disorder (Werner's syndrome) has promulgated the hypothesis that heterochromatin may not be an integral structure of chromosomes, but rather serves as a surface feature or covering. Furthermore, heterochromatin in Werner's syndrome chromosomes was found to be unstable and easily sloughed-off the chromosome surface. In this investigation evidence is presented which shows that incorporation of bromodeoxyuridine into DNA causes instability in the purported heterochromatin covering, resulting in translocation of segments of heterochromatin from the unifilarly-substituted chromatid to the bifilarly-substituted sister chromatid. Such translocation may represent the long-elusive mechanism of sister chromatid exchange formation.