Functional interactions of DNA topoisomerases with a human replication origin.
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.
Abdurashidova
Gulnara
G
Molecular Biology Group, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Radulescu
Sorina
S
Sandoval
Oscar
O
Zahariev
Sotir
S
Danailov
Miltcho B
MB
Demidovich
Alexander
A
Santamaria
Laura
L
Biamonti
Giuseppe
G
Riva
Silvano
S
Falaschi
Arturo
A
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*
D034921:Lamin Type B; D051738:Origin Recognition Complex; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D001973:Bromodeoxyuridine