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Chromatin-bound cGA...
Chromatin-bound cGAS is an inhibitor of DNA repair and hence accelerates genome destabilization and cell death
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- Jiang, Hui (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR)
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Xue, Xiaoyu (författare)
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- Panda, Swarupa, 1985- (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR)
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Kawale, Ajinkya (författare)
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Hooy, Richard M. (författare)
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Liang, Fengshan (författare)
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Sohn, Jungsan (författare)
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Sung, Patrick (författare)
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- Gekara, Nelson O. (författare)
- Umeå universitet,Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Umeå University, Sweden,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
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(creator_code:org_t)
- 2019-09-23
- 2019
- Engelska.
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Ingår i: EMBO Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 38:21
- Relaterad länk:
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https://doi.org/10.1...
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- DNA repair via homologous recombination (HR) is indispensable for genome integrity and cell survival but if unrestrained can result in undesired chromosomal rearrangements. The regulatory mechanisms of HR are not fully understood. Cyclic GMP-AMP synthase (cGAS) is best known as a cytosolic innate immune sensor critical for the outcome of infections, inflammatory diseases, and cancer. Here, we report that cGAS is primarily a chromatin-bound protein that inhibits DNA repair by HR, thereby accelerating genome destabilization, micronucleus generation, and cell death under conditions of genomic stress. This function is independent of the canonical STING-dependent innate immune activation and is physiologically relevant for irradiation-induced depletion of bone marrow cells in mice. Mechanistically, we demonstrate that inhibition of HR repair by cGAS is linked to its ability to self-oligomerize, causing compaction of bound template dsDNA into a higher-ordered state less amenable to strand invasion by RAD51-coated ssDNA filaments. This previously unknown role of cGAS has implications for understanding its involvement in genome instability-associated disorders including cancer.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- cancer
- cell death
- cGAS
- chromatin compaction
- DNA repair
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Jiang, Hui
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Xue, Xiaoyu
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Panda, Swarupa, ...
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Kawale, Ajinkya
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Hooy, Richard M.
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Liang, Fengshan
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visa fler...
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Sohn, Jungsan
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Sung, Patrick
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Gekara, Nelson O ...
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Biokemi och mole ...
- Artiklar i publikationen
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EMBO Journal
- Av lärosätet
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Stockholms universitet
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Umeå universitet