RT Journal Article
SR Electronic
T1 Mitotic progression, arrest, exit or death is determined by centromere integrity and independent of de novo transcription
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 287151
DO 10.1101/287151
A1 Marco Novais-Cruz
A1 Maria Alba Abad
A1 Wilfred F.J. van Ijcken
A1 Niels Galjart
A1 A. Arockia Jeyaprakash
A1 Helder Maiato
A1 Cristina Ferrás
YR 2018
UL http://biorxiv.org/content/early/2018/03/22/287151.abstract
AB Recent studies have challenged the prevailing dogma that transcription is repressed during mitosis. Transcription was also proposed to sustain the spindle assembly checkpoint (SAC) for several hours in response to unattached kinetochores. Here we used live-cell imaging of human cells in culture, combined with 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 robustness and cell fate. However, we were unable to detect significant changes in transcript levels. Moreover, inhibition of transcription independently of DNA intercalation had no effect on SAC response, mitotic progression, exit or death. Mechanistically, we show that DNA intercalating agents reduce the interaction of the CPC with nucleosomes. Thus, the capacity of human cells to progress, sustain, exit or die in mitosis relies on centromere integrity, rather than de novo transcription.