Human Topoisomerase IIalpha: Targeting to Subchromosomal Sites of Activity During Interphase and Mitosis

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2004 Feb 24

PMID 14978217

Citations 20

Authors

Marta Agostinho

Jose Rino

Jose Braga

Fernando Ferreira

Soren Steffensen

Joao Ferreira

Affiliations

Soon will be listed here.

Abstract

Mammalian topoisomerase IIalpha (topo IIalpha) plays a vital role in the removal of topological complexities left on DNA during S phase. Here, we developed a new assay to selectively identify sites of catalytic activity of topo IIalpha with subcellular resolution. We show that topo IIalpha activity concentrates at replicating heterochromatin in late S in a replication-dependent manner and at centric heterochromatin during G2 and M phases. Inhibitor studies indicate that this cell cycle-dependent concentration over heterochromatin is sensitive to chromatin structure. We further show that catalytically active topo IIalpha concentrates along the longitudinal axis of mitotic chromosomes. Finally, we found that catalytically inert forms of the enzyme localize predominantly to splicing speckles in a dynamic manner and that this pool is differentially sensitive to changes in the activities of topo IIalpha itself and RNA polymerase II. Together, our data implicate several previously unsuspected activities in the partitioning of the enzyme between sites of activity and putative depots.

Citing Articles

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Topoisomerase II-Induced Chromosome Breakage and Translocation Is Determined by Chromosome Architecture and Transcriptional Activity.

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