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Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage

Foreign and self-cytoplasmic DNA are recognized by numerous DNA sensor molecules leading to the production of type I interferons. Such DNA agonists should be degraded otherwise cells would be chronically stressed. Most human APOBEC3 cytidine deaminases can initiate catabolism of cytoplasmic mitochon...

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Autores principales: Suspène, Rodolphe, Mussil, Bianka, Laude, Hélène, Caval, Vincent, Berry, Noémie, Bouzidi, Mohamed S., Thiers, Valérie, Wain-Hobson, Simon, Vartanian, Jean-Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389686/
https://www.ncbi.nlm.nih.gov/pubmed/28100701
http://dx.doi.org/10.1093/nar/gkx001
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author Suspène, Rodolphe
Mussil, Bianka
Laude, Hélène
Caval, Vincent
Berry, Noémie
Bouzidi, Mohamed S.
Thiers, Valérie
Wain-Hobson, Simon
Vartanian, Jean-Pierre
author_facet Suspène, Rodolphe
Mussil, Bianka
Laude, Hélène
Caval, Vincent
Berry, Noémie
Bouzidi, Mohamed S.
Thiers, Valérie
Wain-Hobson, Simon
Vartanian, Jean-Pierre
author_sort Suspène, Rodolphe
collection PubMed
description Foreign and self-cytoplasmic DNA are recognized by numerous DNA sensor molecules leading to the production of type I interferons. Such DNA agonists should be degraded otherwise cells would be chronically stressed. Most human APOBEC3 cytidine deaminases can initiate catabolism of cytoplasmic mitochondrial DNA. Using the human myeloid cell line THP-1 with an interferon inducible APOBEC3A gene, we show that cytoplasmic DNA triggers interferon α and β production through the RNA polymerase III transcription/RIG-I pathway leading to massive upregulation of APOBEC3A. By catalyzing C→U editing in single stranded DNA fragments, the enzyme prevents them from re-annealing so attenuating the danger signal. The price to pay is chromosomal DNA damage in the form of CG→TA mutations and double stranded DNA breaks which, in the context of chronic inflammation, could drive cells down the path toward cancer.
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spelling pubmed-53896862017-04-24 Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage Suspène, Rodolphe Mussil, Bianka Laude, Hélène Caval, Vincent Berry, Noémie Bouzidi, Mohamed S. Thiers, Valérie Wain-Hobson, Simon Vartanian, Jean-Pierre Nucleic Acids Res Genome Integrity, Repair and Replication Foreign and self-cytoplasmic DNA are recognized by numerous DNA sensor molecules leading to the production of type I interferons. Such DNA agonists should be degraded otherwise cells would be chronically stressed. Most human APOBEC3 cytidine deaminases can initiate catabolism of cytoplasmic mitochondrial DNA. Using the human myeloid cell line THP-1 with an interferon inducible APOBEC3A gene, we show that cytoplasmic DNA triggers interferon α and β production through the RNA polymerase III transcription/RIG-I pathway leading to massive upregulation of APOBEC3A. By catalyzing C→U editing in single stranded DNA fragments, the enzyme prevents them from re-annealing so attenuating the danger signal. The price to pay is chromosomal DNA damage in the form of CG→TA mutations and double stranded DNA breaks which, in the context of chronic inflammation, could drive cells down the path toward cancer. Oxford University Press 2017-04-07 2017-01-18 /pmc/articles/PMC5389686/ /pubmed/28100701 http://dx.doi.org/10.1093/nar/gkx001 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Genome Integrity, Repair and Replication
Suspène, Rodolphe
Mussil, Bianka
Laude, Hélène
Caval, Vincent
Berry, Noémie
Bouzidi, Mohamed S.
Thiers, Valérie
Wain-Hobson, Simon
Vartanian, Jean-Pierre
Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage
title Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage
title_full Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage
title_fullStr Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage
title_full_unstemmed Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage
title_short Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage
title_sort self-cytoplasmic dna upregulates the mutator enzyme apobec3a leading to chromosomal dna damage
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389686/
https://www.ncbi.nlm.nih.gov/pubmed/28100701
http://dx.doi.org/10.1093/nar/gkx001
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