Topo IIα mobility may help it to resolve chromosomal strain.

Beginning on page 23, Tavormina et al. describe the localization of topoisomerase IIα in living cells undergoing mitosis. Although previous work has suggested that this essential enzyme forms a stable scaffold along mitotic chromosomes, the new study contradicts this model, and provides a detailed view of the protein's highly dynamic movements.

The authors produced a stable cell line expressing fluorescently tagged topoisomerase IIα, and found that during mitosis, the enzyme exchanges rapidly between a cytoplasmic pool and a pool bound to the chromosomes and kinetochores. Interfering with topoisomerase IIα catalytic activity blocks this rapid exchange. On the chromosomes, the protein appears to be concentrated toward the axes of chromosome arms, rather than being uniformly distributed across the arms. In late anaphase and telophase, topoisomerase IIα moves to discrete cytoplasmic foci that appear to incorporate into reforming nuclei.

Though the data do not rule out a possible structural function for topoisomerase IIα, the bulk of the chromosome-associated protein pool is clearly not static. The authors suggest that the rapid turnover may allow the enzyme to quickly reach and relieve areas of chromosomal strain that develop during mitosis. ▪