Nuclear AIM2‐Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair

Abstract Radiation is an essential preparative procedure for bone marrow (BM) transplantation and cancer treatment. The therapeutic efficacy of radiation and associated toxicity varies from patient to patient, making it difficult to prescribe an optimal patient‐specific irradiation dose. The molecul...

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Autores principales:	Hui Jiang, Patrycja Swacha, Nelson O. Gekara
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	AIM2‐like receptors cancer chemotherapy chromatin compaction DNA repair inflammasome Science Q
Acceso en línea:	https://doaj.org/article/f2e0a5c984244060b324bbb5cc791d9a
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spelling	oai:doaj.org-article:f2e0a5c984244060b324bbb5cc791d9a2021-11-17T08:40:31ZNuclear AIM2‐Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair2198-384410.1002/advs.202102534https://doaj.org/article/f2e0a5c984244060b324bbb5cc791d9a2021-11-01T00:00:00Zhttps://doi.org/10.1002/advs.202102534https://doaj.org/toc/2198-3844Abstract Radiation is an essential preparative procedure for bone marrow (BM) transplantation and cancer treatment. The therapeutic efficacy of radiation and associated toxicity varies from patient to patient, making it difficult to prescribe an optimal patient‐specific irradiation dose. The molecular determinants of radiation response remain unclear. AIM2‐like receptors (ALRs) are key players in innate immunity and determine the course of infections, inflammatory diseases, senescence, and cancer. Here it is reported that mice lacking ALRs are resistant to irradiation‐induced BM injury. It is shown that nuclear ALRs are inhibitors of DNA repair, thereby accelerate genome destabilization, micronuclei generation, and cell death, and that this novel function is uncoupled from their role in innate immunity. Mechanistically, ALRs bind to and interfere with chromatin decompaction vital for DNA repair. The finding uncovers ALRs as targets for new interventions against genotoxic tissue injury and as possible biomarkers for predicting the outcome of radio/chemotherapy.Hui JiangPatrycja SwachaNelson O. GekaraWileyarticleAIM2‐like receptorscancerchemotherapychromatin compactionDNA repairinflammasomeScienceQENAdvanced Science, Vol 8, Iss 22, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AIM2‐like receptors cancer chemotherapy chromatin compaction DNA repair inflammasome Science Q
spellingShingle	AIM2‐like receptors cancer chemotherapy chromatin compaction DNA repair inflammasome Science Q Hui Jiang Patrycja Swacha Nelson O. Gekara Nuclear AIM2‐Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair
description	Abstract Radiation is an essential preparative procedure for bone marrow (BM) transplantation and cancer treatment. The therapeutic efficacy of radiation and associated toxicity varies from patient to patient, making it difficult to prescribe an optimal patient‐specific irradiation dose. The molecular determinants of radiation response remain unclear. AIM2‐like receptors (ALRs) are key players in innate immunity and determine the course of infections, inflammatory diseases, senescence, and cancer. Here it is reported that mice lacking ALRs are resistant to irradiation‐induced BM injury. It is shown that nuclear ALRs are inhibitors of DNA repair, thereby accelerate genome destabilization, micronuclei generation, and cell death, and that this novel function is uncoupled from their role in innate immunity. Mechanistically, ALRs bind to and interfere with chromatin decompaction vital for DNA repair. The finding uncovers ALRs as targets for new interventions against genotoxic tissue injury and as possible biomarkers for predicting the outcome of radio/chemotherapy.
format	article
author	Hui Jiang Patrycja Swacha Nelson O. Gekara
author_facet	Hui Jiang Patrycja Swacha Nelson O. Gekara
author_sort	Hui Jiang
title	Nuclear AIM2‐Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair
title_short	Nuclear AIM2‐Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair
title_full	Nuclear AIM2‐Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair
title_fullStr	Nuclear AIM2‐Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair
title_full_unstemmed	Nuclear AIM2‐Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair
title_sort	nuclear aim2‐like receptors drive genotoxic tissue injury by inhibiting dna repair
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/f2e0a5c984244060b324bbb5cc791d9a
work_keys_str_mv	AT huijiang nuclearaim2likereceptorsdrivegenotoxictissueinjurybyinhibitingdnarepair AT patrycjaswacha nuclearaim2likereceptorsdrivegenotoxictissueinjurybyinhibitingdnarepair AT nelsonogekara nuclearaim2likereceptorsdrivegenotoxictissueinjurybyinhibitingdnarepair
_version_	1718425709051904000

Nuclear AIM2‐Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair

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