Mitotic progression, arrest, exit or death relies on centromere structural integrity, rather than de novo transcription

eLife

Maria Alba Abad¹  Niels Galjart²  Marco Novais-Cruz³  Cristina Ferrás³  A Arockia Jeyaprakash⁴  Helder Maiato⁵  Wilfred FJ van IJcken⁵ 

[1] Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal;Center for Biomics, Erasmus Medical Center, Rotterdam, Netherlands;Chromosome Instability & Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal;Department of Cell Biology, Erasmus Medical Center, Rotterdam, Netherlands;Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom;

关键词: mitosis;    transcription;    spindle assembly checkpoint;    Aurora B;    kinetochore;    centromere;   

DOI  :  10.7554/eLife.36898

来源: DOAJ

【 摘 要 】

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 signaling 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.

【 授权许可】

Unknown