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Cohesin-mediated DNA loop extrusion resolves sister chromatids in G2 phase

View ORCID ProfilePaul Batty, Christoph C.H. Langer, Zsuzsanna Takács, Wen Tang, Claudia Blaukopf, Jan-Michael Peters, View ORCID ProfileDaniel W. Gerlich
doi: https://doi.org/10.1101/2023.01.12.523718
Paul Batty
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria
2Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, A-1030, Vienna, Austria
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  • For correspondence: paul.batty@imba.oeaw.ac.at daniel.gerlich@imba.oeaw.ac.at
Christoph C.H. Langer
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria
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Zsuzsanna Takács
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria
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Wen Tang
3Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, 1030 Vienna, Austria
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Claudia Blaukopf
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria
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Jan-Michael Peters
3Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, 1030 Vienna, Austria
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Daniel W. Gerlich
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria
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  • ORCID record for Daniel W. Gerlich
  • For correspondence: paul.batty@imba.oeaw.ac.at daniel.gerlich@imba.oeaw.ac.at
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Abstract

Genetic information is stored in linear DNA molecules, which fold extensively inside cells. DNA replication along the folded template path yields two sister chromatids that initially occupy the same nuclear region in a highly intertwined arrangement. Dividing cells must disentangle and condense the sister chromatids into separate bodies such that a microtubule-based spindle can move them to opposite poles. While the spindle-mediated transport of sister chromatids has been studied in detail, the chromosome-intrinsic mechanics pre-segregating sister chromatids have remained elusive. Here, we show that human sister chromatids resolve extensively already during interphase, in a process dependent on the loop-extruding activity of cohesin, but not that of condensins. Increasing cohesin’s looping capability increases sister DNA resolution in interphase nuclei to an extent normally seen only during mitosis, despite the presence of abundant arm cohesion. That cohesin can resolve sister chromatids so extensively in the absence of mitosis-specific activities indicates that DNA loop extrusion is a generic mechanism for segregating replicated genomes, shared across different Structural Maintenance of Chromosomes (SMC) protein complexes in all kingdoms of life.

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. It is made available under a CC-BY-ND 4.0 International license.
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Posted January 12, 2023.
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Cohesin-mediated DNA loop extrusion resolves sister chromatids in G2 phase
Paul Batty, Christoph C.H. Langer, Zsuzsanna Takács, Wen Tang, Claudia Blaukopf, Jan-Michael Peters, Daniel W. Gerlich
bioRxiv 2023.01.12.523718; doi: https://doi.org/10.1101/2023.01.12.523718
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Cohesin-mediated DNA loop extrusion resolves sister chromatids in G2 phase
Paul Batty, Christoph C.H. Langer, Zsuzsanna Takács, Wen Tang, Claudia Blaukopf, Jan-Michael Peters, Daniel W. Gerlich
bioRxiv 2023.01.12.523718; doi: https://doi.org/10.1101/2023.01.12.523718

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