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A novel chromatin tether domain controls topoisomerase II? dynamics and mitotic chromosome formation.

ABSTRACT: DNA topoisomerase II? (Topo II?) 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 II? on chromatin in mitosis and is necessary for the formation of mitotic chromosomes. Our data suggest that the dynamics of Topo II? on chromosomes are important for successful mitosis and implicate histone tail posttranslational modifications in regulating Topo II?.

SUBMITTER: Lane AB

PROVIDER: S-EPMC3824022 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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

Lane Andrew B AB Giménez-Abián Juan F JF Clarke Duncan J DJ

The Journal of cell biology 20131101 3

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 mito ...[more]

PMID: 24217621

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

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