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Inversion of asymmetric histone deposition upon replication stress

Martijn R. H. Zwinderman, Thamar Jessurun Lobo, Petra E. van der Wouden, Diana C. J. Spierings, Marcel A. T. M. van Vugt, Peter M. Lansdorp, View ORCID ProfileVictor Guryev, View ORCID ProfileFrank J. Dekker
doi: https://doi.org/10.1101/2021.04.20.440573
Martijn R. H. Zwinderman
1Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands
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Thamar Jessurun Lobo
2European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands
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Petra E. van der Wouden
1Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands
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Diana C. J. Spierings
2European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands
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Marcel A. T. M. van Vugt
3Department of Medical Oncology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
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Peter M. Lansdorp
2European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands
4Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, V5Z 1L3 British Columbia, Canada
5Department of Medical Genetics, University of British Columbia, Vancouver, V6T 1Z4 British Columbia, Canada
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Victor Guryev
2European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands
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  • ORCID record for Victor Guryev
Frank J. Dekker
1Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands
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  • For correspondence: f.j.dekker@rug.nl
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Abstract

Following DNA replication, equal amounts of histones are distributed over sister chromatids by re-deposition of parental histones and deposition of newly synthesized histones. Molecular mechanisms balancing the allocation of new and old histones remain largely unknown. Here, we studied the genome-wide distribution of new histones relative to parental DNA template strands and replication initiation zones using double-click-seq. In control conditions, new histones were preferentially found on DNA replicated by the lagging strand machinery. Strikingly, replication stress induced by hydroxyurea or curaxin treatment, and inhibition of ATR or p53 inactivation, inverted the observed histone deposition bias to the strand replicated by the leading strand polymerase in line with previously reported effects on RPA occupancy. We propose that asymmetric deposition of newly synthesized histones onto sister chromatids reflects differences in the processivity of leading and lagging strand synthesis.

Footnotes

  • ↵‡ These authors should be regarded as joint senior authors of the manuscript

  • ↵* Lead Contact

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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 4.0 International license.
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Posted April 21, 2021.
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Inversion of asymmetric histone deposition upon replication stress
Martijn R. H. Zwinderman, Thamar Jessurun Lobo, Petra E. van der Wouden, Diana C. J. Spierings, Marcel A. T. M. van Vugt, Peter M. Lansdorp, Victor Guryev, Frank J. Dekker
bioRxiv 2021.04.20.440573; doi: https://doi.org/10.1101/2021.04.20.440573
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Inversion of asymmetric histone deposition upon replication stress
Martijn R. H. Zwinderman, Thamar Jessurun Lobo, Petra E. van der Wouden, Diana C. J. Spierings, Marcel A. T. M. van Vugt, Peter M. Lansdorp, Victor Guryev, Frank J. Dekker
bioRxiv 2021.04.20.440573; doi: https://doi.org/10.1101/2021.04.20.440573

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