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Functional interactions of DNA topoisomerases with a human replication origin
Author(s) -
Abdurashidova Gulnara,
Radulescu Sorina,
Sandoval Oscar,
Zahariev Sotir,
Danailov Miltcho B,
Demidovich Alexander,
Santamaria Laura,
Biamonti Giuseppe,
Riva Silvano,
Falaschi Arturo
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601578
Subject(s) - biology , molecular genetics , library science , humanities , genetics , gene , philosophy , computer science
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.