Aclarubicin Reduces the Nuclear Mobility of Human DNA Topoisomerase IIβ

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Oct 16

PMID 39409010

Authors

Keiko Morotomi-Yano

Ken-Ichi Yano

Affiliations

Soon will be listed here.

Abstract

DNA topoisomerase II (TOP2) is an enzyme that resolves DNA topological problems arising in various nuclear processes, such as transcription. Aclarubicin, a member of the anthracyclines, is known to prevent the association of TOP2 with DNA, inhibiting the early step of TOP2 catalytic reactions. During our research on the subnuclear distribution of human TOP2B, we found that aclarubicin affects the mobility of TOP2B in the nucleus. FRAP analysis demonstrated that aclarubicin decreased the nuclear mobility of EGFP-tagged TOP2B in a concentration-dependent manner. Aclarubicin exerted its inhibitory effects independently of TOP2B enzymatic activities: TOP2B mutants defective for either ATPase or topoisomerase activity also exhibited reduced nuclear mobility in the presence of aclarubicin. Immunofluorescence analysis showed that aclarubicin antagonized the induction of DNA damage by etoposide. Although the prevention of the TOP2-DNA association is generally considered a primary action of aclarubicin in TOP2 inhibition, our findings highlight a previously unanticipated effect of aclarubicin on TOP2B in the cellular environment.

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