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Alerting the immune system to DNA damage: micronuclei as mediators

Healthy cells experience thousands of DNA lesions per day during normal cellular metabolism, and ionizing radiation and chemotherapeutic drugs rely on DNA damage to kill cancer cells. In response to such lesions, the DNA damage response (DDR) activates cell-cycle checkpoints, initiates DNA repair me...

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Detalles Bibliográficos
Autores principales: MacDonald, Kate M., Benguerfi, Soraya, Harding, Shane M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588664/
https://www.ncbi.nlm.nih.gov/pubmed/32844183
http://dx.doi.org/10.1042/EBC20200016
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author MacDonald, Kate M.
Benguerfi, Soraya
Harding, Shane M.
author_facet MacDonald, Kate M.
Benguerfi, Soraya
Harding, Shane M.
author_sort MacDonald, Kate M.
collection PubMed
description Healthy cells experience thousands of DNA lesions per day during normal cellular metabolism, and ionizing radiation and chemotherapeutic drugs rely on DNA damage to kill cancer cells. In response to such lesions, the DNA damage response (DDR) activates cell-cycle checkpoints, initiates DNA repair mechanisms, or promotes the clearance of irreparable cells. Work over the past decade has revealed broader influences of the DDR, involving inflammatory gene expression following unresolved DNA damage, and immune surveillance of damaged or mutated cells. Subcellular structures called micronuclei, containing broken fragments of DNA or whole chromosomes that have been isolated away from the rest of the genome, are now recognized as one mediator of DDR-associated immune recognition. Micronuclei can initiate pro-inflammatory signaling cascades, or massively degrade to invoke distinct forms of genomic instability. In this mini-review, we aim to provide an overview of the current evidence linking the DDR to activation of the immune response through micronuclei formation, identifying key areas of interest, open questions, and emerging implications.
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spelling pubmed-75886642020-10-30 Alerting the immune system to DNA damage: micronuclei as mediators MacDonald, Kate M. Benguerfi, Soraya Harding, Shane M. Essays Biochem Cancer Healthy cells experience thousands of DNA lesions per day during normal cellular metabolism, and ionizing radiation and chemotherapeutic drugs rely on DNA damage to kill cancer cells. In response to such lesions, the DNA damage response (DDR) activates cell-cycle checkpoints, initiates DNA repair mechanisms, or promotes the clearance of irreparable cells. Work over the past decade has revealed broader influences of the DDR, involving inflammatory gene expression following unresolved DNA damage, and immune surveillance of damaged or mutated cells. Subcellular structures called micronuclei, containing broken fragments of DNA or whole chromosomes that have been isolated away from the rest of the genome, are now recognized as one mediator of DDR-associated immune recognition. Micronuclei can initiate pro-inflammatory signaling cascades, or massively degrade to invoke distinct forms of genomic instability. In this mini-review, we aim to provide an overview of the current evidence linking the DDR to activation of the immune response through micronuclei formation, identifying key areas of interest, open questions, and emerging implications. Portland Press Ltd. 2020-10 2020-08-26 /pmc/articles/PMC7588664/ /pubmed/32844183 http://dx.doi.org/10.1042/EBC20200016 Text en © 2020 The Author(s). https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).
spellingShingle Cancer
MacDonald, Kate M.
Benguerfi, Soraya
Harding, Shane M.
Alerting the immune system to DNA damage: micronuclei as mediators
title Alerting the immune system to DNA damage: micronuclei as mediators
title_full Alerting the immune system to DNA damage: micronuclei as mediators
title_fullStr Alerting the immune system to DNA damage: micronuclei as mediators
title_full_unstemmed Alerting the immune system to DNA damage: micronuclei as mediators
title_short Alerting the immune system to DNA damage: micronuclei as mediators
title_sort alerting the immune system to dna damage: micronuclei as mediators
topic Cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588664/
https://www.ncbi.nlm.nih.gov/pubmed/32844183
http://dx.doi.org/10.1042/EBC20200016
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