2. Academic Validation
  3. Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1

Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1

  • Mol Cell. 2021 Dec 16;81(24):5007-5024.e9. doi: 10.1016/j.molcel.2021.10.015.
Anika Wiegard 1,  Vladislav Kuzin 1,  Donald P Cameron 1,  Jan Grosser 1,  Michele Ceribelli 2,  Rashid Mehmood 3,  Roberto Ballarino 4,  Francesco Valant 1,  Radosław Grochowski 4,  Ivana Karabogdan 5,  Nicola Crosetto 4,  Arne Lindqvist 1,  Anna Helene Bizard 6,  Fedor Kouzine 7,  Toyoaki Natsume 8,  Laura Baranello 9
Affiliations

Affiliations

  • 1 Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
  • 2 Division of Pre-Clinical Innovation, NCATS, National Institutes of Health, Rockville, MD 20850, USA.
  • 3 Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden; Department of Software Engineering, University of Kotli, AJ&K, 45320 Kotli Azad Kashmir, Pakistan.
  • 4 Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17165 Stockholm, Sweden.
  • 5 German Cancer Research Center, DKFZ, 69120 Heidelberg, Germany.
  • 6 Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.
  • 7 Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • 8 Department of Chromosome Science, National Institute of Genetics, Shizuoka 411-8540, Japan; Research Center for Genome & Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
  • 9 Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden. Electronic address: laura.baranello@ki.se.
PMID: 34767771 DOI: 10.1016/j.molcel.2021.10.015
Abstract

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.

Keywords

ChIP-seq; RNAPII; TOP1; cell cycle; mitosis; polymerase; segregation; supercoiling; topoisomerase; transcription.

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