Interaction of the BLM protein with Topo III alpha in Somatic and meiotic cells

Abstract

Bloom syndrome (BS) is characterized by genomic instability and cancer susceptibility. The gene defective in BS, BLM, encodes a DNA helicase of the RecQ family. Sgslp, a RecQ-family helicase in S. cerevisiae, interacts physically and functionally with the topoisomerase III protein. Using coimmunoprecipitation and immunolocalization, we demonstrate in somatic human cells an association between BLM and the topoisomerase Topo III alpha and between Topo III alpha and RECQL, another RecQ family helicase. In fibroblasts, these three proteins colocalize in PML nuclear bodies (NBs). Localization of Topo III alpha to NBs is disrupted in BS cells, indicating that BLM is necessary for the proper localization of Topo III alpha and suggesting that NBs may be an important site of function for these proteins. BLM and Topo III alpha also colocalize in meiosis, in foci on the lateral elements of recently synapsed homologous chromosomes. Thus the genome instability observed in BS may involve perturbations in the activities of DNA topoisomerases, in addition to defects in BLM itself.

This chapter is a modified version of a manuscript representing an equal contribution between Brad Johnson and myself. Much of the data in this chapter has been previously published: Johnson FB, Lombard DB, Neff NF et al (2000). Association of the Bloom syndrome protein with topoisomerase III alpha in somatic and meiotic cells. Cancer Res 60:1162–1167. Used by permission.