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The N-Terminal Domain of cGAS Determines Preferential Association with Centromeric DNA and Innate Immune Activation in the Nucleus

Authors
  • Gentili, Matteo1
  • Lahaye, Xavier1
  • Nadalin, Francesca1
  • Nader, Guilherme F.P.2, 3
  • Puig Lombardi, Emilia4
  • Herve, Solène2
  • De Silva, Nilushi S.1
  • Rookhuizen, Derek C.1
  • Zueva, Elina1
  • Goudot, Christel1
  • Maurin, Mathieu1
  • Bochnakian, Aurore1
  • Amigorena, Sebastian1
  • Piel, Matthieu2, 3
  • Fachinetti, Daniele2
  • Londoño-Vallejo, Arturo4
  • Manel, Nicolas1
  • 1 Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France
  • 2 Institut Curie, PSL Research University, CNRS, UMR 144, 75005 Paris, France
  • 3 Institut Pierre-Gilles de Gennes, PSL Research University, 75005 Paris, France
  • 4 Institut Curie, PSL Research University, Sorbonne Universités, CNRS, UMR 3244 Telomere and Cancer Lab, 75005 Paris, France
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Feb 26, 2019
Volume
26
Issue
9
Pages
2377–2393
Identifiers
DOI: 10.1016/j.celrep.2019.01.105
PMID: 30811988
PMCID: PMC6391843
Source
PubMed Central
Keywords
License
Unknown

Abstract

cGAS is a well-established innate immune sensor of cytosolic DNA, but its presence in the nucleus is poorly understood. Gentili et al. find that nuclear cGAS is active and enriched on centromeres and LINE DNA repeats. Nuclear-cytoplasmic distribution, centromere association, and nuclear activation are determined by its non-enzymatic N-terminal domain.

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