title: Chromosome breakage is regulated by the interaction of the BLM helicase and topoisomerase IIalpha.
abstract: 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 IIα interact directly via amino acids 489-587 of BLM and colocalize predominantly in late G2 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 IIα-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 IIα 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.
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine, Columbus, Ohio 45229, USA.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Russell
authors.forename: Saumitri
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Jeremy
authors.initials: J
authors.lastname: Keirsey
authors.forename: April
authors.initials: A
authors.lastname: Sandy
authors.forename: Patrick
authors.initials: P
authors.lastname: Grierson
authors.forename: Erin
authors.initials: E
authors.lastname: Perchiniak
authors.forename: Juraj
authors.initials: J
authors.lastname: Kavecansky
authors.forename: Samir
authors.initials: S
authors.lastname: Acharya
authors.forename: Joanna
authors.initials: J
authors.lastname: Groden
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D019457:Chromosome Breakage; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016195:G2 Phase / Q000502:physiology; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C097151:Bloom syndrome protein; D053484:RecQ Helicases; D004250:DNA Topoisomerases, Type II