A novel chromatin tether domain controls topoisomerase IIα dynamics and mitotic chromosome formation
نویسندگان
چکیده
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.
منابع مشابه
The α isoform of topoisomerase II is required for hypercompaction of mitotic chromosomes in human cells
As proliferating cells transit from interphase into M-phase, chromatin undergoes extensive reorganization, and topoisomerase (topo) IIα, the major isoform of this enzyme present in cycling vertebrate cells, plays a key role in this process. In this study, a human cell line conditional null mutant for topo IIα and a derivative expressing an auxin-inducible degron (AID)-tagged version of the prot...
متن کاملMitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase IIα
Mitotic chromosome formation involves a relatively minor condensation of the chromatin volume coupled with a dramatic reorganization into the characteristic "X" shape. Here we report results of a detailed morphological analysis, which revealed that chromokinesin KIF4 cooperated in a parallel pathway with condensin complexes to promote the lateral compaction of chromatid arms. In this analysis, ...
متن کاملSmc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells
The structural maintenance of chromosomes (SMC) proteins constitute the core of critical complexes involved in structural organization of chromosomes. In yeast, the Smc5/6 complex is known to mediate repair of DNA breaks and replication of repetitive genomic regions, including ribosomal DNA loci and telomeres. In mammalian cells, which have diverse genome structure and scale from yeast, the Smc...
متن کاملNew insight into the mitotic chromosome structure: irregular folding of nucleosome fibers without 30-nm chromatin structure.
Mitotic chromosomes are essential structures for the faithful transmission of replicated genomic DNA into two daughter cells during cell division. A long strand of DNA is wrapped around a core histone and forms a nucleosome. The nucleosome has long been assumed to be folded into 30-nm chromatin fibers. However, how the nucleosome or 30-nm chromatin fiber is organized into mitotic chromosomes re...
متن کاملDynamic localization of SMC5/6 complex proteins during mammalian meiosis and mitosis suggests functions in distinct chromosome processes.
Four members of the structural maintenance of chromosome (SMC) protein family have essential functions in chromosome condensation (SMC2/4) and sister-chromatid cohesion (SMC1/3). The SMC5/6 complex has been implicated in chromosome replication, DNA repair and chromosome segregation in somatic cells, but its possible functions during mammalian meiosis are unknown. Here, we show in mouse spermato...
متن کامل