Mitotic progression, arrest, exit or death relies on centromere structural integrity, rather than de novo transcription
- Universidade do Porto, Portugal
- University of Edinburgh, United Kingdom
- Erasmus Medical Center, Netherlands
Abstract
Recent studies have challenged the prevailing dogma that transcription is repressed during mitosis. Transcription was also proposed to sustain a robust spindle assembly checkpoint (SAC) response. Here we used live-cell imaging of human cells, RNA-seq and qPCR to investigate the requirement for de novo transcription during mitosis. Under conditions of persistently unattached kinetochores, transcription inhibition with actinomycin D, or treatment with other DNA-intercalating drugs, delocalized the chromosomal passenger complex (CPC) protein Aurora B from centromeres, compromising SAC signalling and cell fate. However, we were unable to detect significant changes in mitotic transcript levels. Moreover, inhibition of transcription independently of DNA intercalation had no effect on Aurora B centromeric localization, SAC response, mitotic progression, exit or death. Mechanistically, we show that DNA intercalating agents reduce the interaction of the CPC with nucleosomes. Thus, mitotic progression, arrest, exit or death is determined by centromere structural integrity, rather than de novo transcription.
Data availability
Processed RNA-seq have been deposited and can be consulted athttps://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-6661
Article and author information
Author details
Wilfred FJ van IJcken
Funding
FEDER-Fundo Europeu de desenvolvimento Regional funds through the COMPETE 2020 (Norte-01-0145-FEDER-000029)
- Cristina Ferrás
FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 (Norte-07-0124-FEDER-000003)
- Cristina Ferrás
Fundação para a Ciência e a Tecnologia (EXPL/IF/00765/2014/CP1241/CT0003)
- Cristina Ferrás
Fundação para a Ciência e a Tecnologia (FCT Investigator grant IF/00765/2014)
- Cristina Ferrás
Fundação para a Ciência e a Tecnologia (FCT PhD grant SFRH/BD/117063/2016)
- Marco Novais-Cruz
European Research Council (CODECHECK)
- Helder Maiato
FLAD Life Science
- Helder Maiato
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Novais-Cruz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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