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1: EMBO J. 2007 Feb 21;26(4):998-1009. Epub 2007 Feb 8.
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Functional interactions of DNA topoisomerases with a human replication origin.

Abdurashidova G, Radulescu S, Sandoval O, Zahariev S, Danailov MB, Demidovich A, Santamaria L, Biamonti G, Riva S, Falaschi A.

Molecular Biology Group, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.

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.

Publication Types:
PMID: 17290216 [PubMed - indexed for MEDLINE]

PMCID: PMC1852844