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Antecedent chromatin organization determines cGAS recruitment to ruptured micronuclei

Author

Listed:
  • Kate M. MacDonald

    (University of Toronto)

  • Shirony Nicholson-Puthenveedu

    (University Health Network)

  • Maha M. Tageldein

    (University of Toronto)

  • Sarika Khasnis

    (University Health Network)

  • Cheryl H. Arrowsmith

    (University of Toronto
    University Health Network
    University of Toronto)

  • Shane M. Harding

    (University of Toronto
    University Health Network
    University of Toronto)

Abstract

Micronuclei (MN) are cytosolic bodies that sequester acentric fragments or mis-segregated chromosomes from the primary nucleus. Spontaneous rupture of the MN envelope allows recognition by the viral receptor cyclic GMP-AMP synthase (cGAS), initiating interferon signaling downstream of DNA damage. Here, we demonstrate that MN rupture is permissive but not sufficient for cGAS localization. Chromatin characteristics such as histone 3, lysine 79 dimethylation (H3K79me2) are present in the nucleus before DNA damage, retained in ruptured MN, and regulate cGAS recruitment. cGAS is further responsive to dynamic intra-MN processes occurring prior to rupture, including transcription. MN chromatin tethering via the nucleosome acidic patch is necessary for cGAS-dependent interferon signaling. Our data suggest that both damage-antecedent nuclear chromatin status and MN-contained chromatin organizational changes dictate cGAS recruitment and the magnitude of the cGAS-driven interferon cascade. Our work defines MN as integrative signaling hubs for the cellular response to genotoxic stress.

Suggested Citation

  • Kate M. MacDonald & Shirony Nicholson-Puthenveedu & Maha M. Tageldein & Sarika Khasnis & Cheryl H. Arrowsmith & Shane M. Harding, 2023. "Antecedent chromatin organization determines cGAS recruitment to ruptured micronuclei," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36195-8
    DOI: 10.1038/s41467-023-36195-8
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    as
    1. Baoyu Zhao & Pengbiao Xu & Chesley M. Rowlett & Tao Jing & Omkar Shinde & Yuanjiu Lei & A. Phillip West & Wenshe Ray Liu & Pingwei Li, 2020. "The molecular basis of tight nuclear tethering and inactivation of cGAS," Nature, Nature, vol. 587(7835), pages 673-677, November.
    2. Gloria Jih & Nahid Iglesias & Mark A. Currie & Natarajan V. Bhanu & Joao A. Paulo & Steven P. Gygi & Benjamin A. Garcia & Danesh Moazed, 2017. "Unique roles for histone H3K9me states in RNAi and heritable silencing of transcription," Nature, Nature, vol. 547(7664), pages 463-467, July.
    3. Wenyu Yu & Emma J. Chory & Amy K. Wernimont & Wolfram Tempel & Alex Scopton & Alexander Federation & Jason J. Marineau & Jun Qi & Dalia Barsyte-Lovejoy & Joanna Yi & Richard Marcellus & Roxana E. Iaco, 2012. "Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
    4. A. Phillip West & William Khoury-Hanold & Matthew Staron & Michal C. Tal & Cristiana M. Pineda & Sabine M. Lang & Megan Bestwick & Brett A. Duguay & Nuno Raimundo & Donna A. MacDuff & Susan M. Kaech &, 2015. "Mitochondrial DNA stress primes the antiviral innate immune response," Nature, Nature, vol. 520(7548), pages 553-557, April.
    5. Claire Vanpouille-Box & Amandine Alard & Molykutty J. Aryankalayil & Yasmeen Sarfraz & Julie M. Diamond & Robert J. Schneider & Giorgio Inghirami & C. Norman Coleman & Silvia C. Formenti & Sandra Dema, 2017. "DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
    6. Shane M. Harding & Joseph L. Benci & Jerome Irianto & Dennis E. Discher & Andy J. Minn & Roger A. Greenberg, 2017. "Mitotic progression following DNA damage enables pattern recognition within micronuclei," Nature, Nature, vol. 548(7668), pages 466-470, August.
    7. Sebastian Scheer & Suzanne Ackloo & Tiago S. Medina & Matthieu Schapira & Fengling Li & Jennifer A. Ward & Andrew M. Lewis & Jeffrey P. Northrop & Paul L. Richardson & H. Ümit Kaniskan & Yudao Shen & , 2019. "A chemical biology toolbox to study protein methyltransferases and epigenetic signaling," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    8. Karen Crasta & Neil J. Ganem & Regina Dagher & Alexandra B. Lantermann & Elena V. Ivanova & Yunfeng Pan & Luigi Nezi & Alexei Protopopov & Dipanjan Chowdhury & David Pellman, 2012. "DNA breaks and chromosome pulverization from errors in mitosis," Nature, Nature, vol. 482(7383), pages 53-58, February.
    9. Felix Wojcik & Geoffrey P. Dann & Leslie Y. Beh & Galia T. Debelouchina & Raphael Hofmann & Tom W. Muir, 2018. "Functional crosstalk between histone H2B ubiquitylation and H2A modifications and variants," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    10. Samuel F. Bakhoum & Bryan Ngo & Ashley M. Laughney & Julie-Ann Cavallo & Charles J. Murphy & Peter Ly & Pragya Shah & Roshan K. Sriram & Thomas B. K. Watkins & Neil K. Taunk & Mercedes Duran & Chantal, 2018. "Chromosomal instability drives metastasis through a cytosolic DNA response," Nature, Nature, vol. 553(7689), pages 467-472, January.
    11. Cheng-Zhong Zhang & Alexander Spektor & Hauke Cornils & Joshua M. Francis & Emily K. Jackson & Shiwei Liu & Matthew Meyerson & David Pellman, 2015. "Chromothripsis from DNA damage in micronuclei," Nature, Nature, vol. 522(7555), pages 179-184, June.
    12. Shiwei Liu & Mijung Kwon & Mark Mannino & Nachen Yang & Fioranna Renda & Alexey Khodjakov & David Pellman, 2018. "Nuclear envelope assembly defects link mitotic errors to chromothripsis," Nature, Nature, vol. 561(7724), pages 551-555, September.
    13. Ganesh R. Pathare & Alexiane Decout & Selene Glück & Simone Cavadini & Kristina Makasheva & Ruud Hovius & Georg Kempf & Joscha Weiss & Zuzanna Kozicka & Baptiste Guey & Pauline Melenec & Beat Fierz & , 2020. "Structural mechanism of cGAS inhibition by the nucleosome," Nature, Nature, vol. 587(7835), pages 668-672, November.
    14. Laura Godfrey & Nicholas T. Crump & Ross Thorne & I-Jun Lau & Emmanouela Repapi & Dimitra Dimou & Alastair L. Smith & Joe R. Harman & Jelena M. Telenius & A. Marieke Oudelaar & Damien J. Downes & Pare, 2019. "DOT1L inhibition reveals a distinct subset of enhancers dependent on H3K79 methylation," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    15. Karen J. Mackenzie & Paula Carroll & Carol-Anne Martin & Olga Murina & Adeline Fluteau & Daniel J. Simpson & Nelly Olova & Hannah Sutcliffe & Jacqueline K. Rainger & Andrea Leitch & Ruby T. Osborn & A, 2017. "cGAS surveillance of micronuclei links genome instability to innate immunity," Nature, Nature, vol. 548(7668), pages 461-465, August.
    16. Shangming Tang & Ema Stokasimov & Yuxiang Cui & David Pellman, 2022. "Breakage of cytoplasmic chromosomes by pathological DNA base excision repair," Nature, Nature, vol. 606(7916), pages 930-936, June.
    17. Sebastian Michalski & Carina C. de Oliveira Mann & Che A. Stafford & Gregor Witte & Joseph Bartho & Katja Lammens & Veit Hornung & Karl-Peter Hopfner, 2020. "Structural basis for sequestration and autoinhibition of cGAS by chromatin," Nature, Nature, vol. 587(7835), pages 678-682, November.
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