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The TFIIH Complex is Required to Establish and Maintain Mitotic Chromosome Structure

View ORCID ProfileJulian Haase, Richard Chen, View ORCID ProfileMary Kate Bonner, Lisa M. Miller Jenkins, View ORCID ProfileAlexander E. Kelly
doi: https://doi.org/10.1101/2021.11.06.467569
Julian Haase
1Laboratory of Biochemistry & Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892
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Richard Chen
1Laboratory of Biochemistry & Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892
2Graduate School of Biomedical Sciences, UT Southwestern Medical Center, Dallas, Texas 75390
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Mary Kate Bonner
1Laboratory of Biochemistry & Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892
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Lisa M. Miller Jenkins
3Laboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892
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Alexander E. Kelly
1Laboratory of Biochemistry & Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892
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  • ORCID record for Alexander E. Kelly
  • For correspondence: alexander.kelly@nih.gov
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Abstract

Condensins compact chromosomes to promote their equal segregation during mitosis, but the mechanism of condensin engagement with and action on chromatin is incompletely understood. Here, we show that the general transcription factor TFIIH complex is continuously required to establish and maintain a compacted chromosome structure in transcriptionally silent Xenopus egg extracts. Inhibiting the DNA-dependent ATPase activity of the TFIIH complex subunit XPB prevents the enrichment of condensins I and II, but not topoisomerase II, on chromatin. In addition, TFIIH inhibition reversibly induces a complete loss of chromosome structure within minutes, prior to the loss of condensins from chromatin. Reducing nucleosome density through partial histone depletion restores chromosome structure and condensin enrichment in the absence of TFIIH activity. We propose that the TFIIH complex promotes mitotic chromosome condensation by dynamically altering chromatin structure to facilitate condensin loading and condensin-dependent loop extrusion.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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Posted November 07, 2021.
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The TFIIH Complex is Required to Establish and Maintain Mitotic Chromosome Structure
Julian Haase, Richard Chen, Mary Kate Bonner, Lisa M. Miller Jenkins, Alexander E. Kelly
bioRxiv 2021.11.06.467569; doi: https://doi.org/10.1101/2021.11.06.467569
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The TFIIH Complex is Required to Establish and Maintain Mitotic Chromosome Structure
Julian Haase, Richard Chen, Mary Kate Bonner, Lisa M. Miller Jenkins, Alexander E. Kelly
bioRxiv 2021.11.06.467569; doi: https://doi.org/10.1101/2021.11.06.467569

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