Journal
MOLECULAR CELL
Volume 81, Issue 24, Pages 5007-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2021.10.015
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Funding
- Wallenberg Foundation (WAF in Medicine 2016)
- Swedish Research Council [2016-02610 VR, 2018-05973]
- Swedish Governmental Agency for Innovation Systems [2016-02055 VINNOVA]
- Karo-linska Institutet (KID)
- Cancerfonden [180608]
- Japan Society for the Promotion of Science (JSPS) KAKENHI [JP19K06495]
- Ragnar Soderberg Foundation (Fellows in Medicine 2016)
- Karolinska In-stitutet (KID)
- Swedish National Infrastructure for Computing (SNIC) at UPPMAX [SNIC 2018/8-390]
- Karolinska Institutet
- Swedish Research Council [2016-02610] Funding Source: Swedish Research Council
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TOP1 is required for assisting transcription during mitosis, with consequences for cell growth and gene expression long after mitosis is completed, ensuring cellular memory is preserved in subsequent generations.
As cells enter mitosis, chromatin compacts to facilitate chromosome segregation yet remains transcribed. Transcription supercoils DNA to levels that can impede further progression of RNA polymerase II (RNAPII) unless it is removed by DNA topoisomerase 1 (TOP1). Using ChIP-seq on mitotic cells, we found that TOP1 is required for RNAPII translocation along genes. The stimulation of TOP1 activity by RNAPII during elongation allowed RNAPII clearance from genes in prometaphase and enabled chromosomal segregation. Disruption of the TOP1-RNAPII interaction impaired RNAPII spiking at promoters and triggered defects in the post-mitotic transcription program. This program includes factors necessary for cell growth, and cells with impaired TOP1-RNAPII interaction are more sensitive to inhibitors of mTOR signaling. We conclude that TOP1 is necessary for assisting transcription during mitosis with consequences for growth and gene expression long after mitosis is completed. In this sense, TOP1 ensures that cellular memory is preserved in subsequent generations.
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