A novel chromatin tether domain controls topoisomerase IIα dynamics and mitotic chromosome formation

Andrew B. Lane, Juan F. Giménez-Abián, Duncan J. Clarke

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

DNA topoisomerase IIα (Topo IIα) is the target of an important class of anticancer drugs, but tumor cells can become resistant by reducing the association of the enzyme with chromosomes. Here we describe a critical mechanism of chromatin recruitment and exchange that relies on a novel chromatin tether (ChT) domain and mediates interaction with histone H3 and DNA. We show that the ChT domain controls the residence time of Topo IIα on chromatin in mitosis and is necessary for the formation of mitotic chromosomes. Our data suggest that the dynamics of Topo IIα on chromosomes are important for successful mitosis and implicate histone tail posttranslational modifications in regulating Topo IIα.

Original languageEnglish (US)
Pages (from-to)471-486
Number of pages16
JournalJournal of Cell Biology
Volume203
Issue number3
DOIs
StatePublished - Nov 11 2013

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