Chromosome Breakage Is Regulated by the Interaction of the BLM Helicase and Topoisomerase IIα

Cells deficient in the recQ-like helicase BLM are characterized by chromosome changes that suggest the disruption of normal mechanisms needed to resolve recombination intermediates and to maintain chromosome stability. Human BLM and topoisomerase II alpha interact directly via amino acids 489-587 of BLM and colocalize predominantly in late G(2) and M phases of the cell cycle. Deletion of this region does not affect the inherent in vitro helicase activity of BLM but inhibits the topoisomerase II alpha-dependent enhancement of its activity, based on the analysis of specific DNA substrates that represent some recombination intermediates. Deletion of the interaction domain from BLM fails to correct the elevated chromosome breakage of transfected BLM-deficient cells. Our results demonstrate that the BLM-topoisomerase II alpha interaction is important for preventing chromosome breakage and elucidate a DNA repair mechanism that is critical to maintain chromosome stability in cells and to prevent tumor formation. Cancer Res; 71(2); 561-71. (C) 2011 AACR.