title: Functional interactions of DNA topoisomerases with a human replication origin.
abstract: The human DNA replication origin, located in the lamin B2 gene, interacts with the DNA topoisomerases I and II in a cell cycle-modulated manner. The topoisomerases interact in vivo and in vitro with precise bonds ahead of the start sites of bidirectional replication, within the pre-replicative complex region; topoisomerase I is bound in M, early G1 and G1/S border and topoisomerase II in M and the middle of G1. The Orc2 protein competes for the same sites of the origin bound by either topoisomerase in different moments of the cell cycle; furthermore, it interacts on the DNA with topoisomerase II during the assembly of the pre-replicative complex and with DNA-bound topoisomerase I at the G1/S border. Inhibition of topoisomerase I activity abolishes origin firing. Thus, the two topoisomerases are closely associated with the replicative complexes, and DNA topology plays an essential functional role in origin activation.
authors.affiliation: Molecular Biology Group, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
authors.forename: Gulnara
authors.initials: G
authors.lastname: Abdurashidova
authors.forename: Sorina
authors.initials: S
authors.lastname: Radulescu
authors.forename: Oscar
authors.initials: O
authors.lastname: Sandoval
authors.forename: Sotir
authors.initials: S
authors.lastname: Zahariev
authors.forename: Miltcho B
authors.initials: MB
authors.lastname: Danailov
authors.forename: Alexander
authors.initials: A
authors.lastname: Demidovich
authors.forename: Laura
authors.initials: L
authors.lastname: Santamaria
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biamonti
authors.forename: Silvano
authors.initials: S
authors.lastname: Riva
authors.forename: Arturo
authors.initials: A
authors.lastname: Falaschi
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D053837:DNA Cleavage; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D051738:Origin Recognition Complex / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D018741:Replication Origin / Q000235:genetics*
chemical_list: D034921:Lamin Type B; D051738:Origin Recognition Complex; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D001973:Bromodeoxyuridine