 |
Journal articles
Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage
Abstract : Foreign and self-cytoplasmic DNA are recognized by numerous DNA sensor molecules leading to the production of type I interferons. Such DNA ago-nists 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 inter-feron and production through the RNA poly-merase 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 chromo-somal 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.
Cited literature [56 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-02065335
Contributor : Florence Jeannot <>
Submitted on : Tuesday, March 12, 2019 - 3:52:06 PM
Last modification on : Monday, April 26, 2021 - 6:14:02 PM
Long-term archiving on: : Thursday, June 13, 2019 - 3:15:28 PM
Contributor : Florence Jeannot <>
Submitted on : Tuesday, March 12, 2019 - 3:52:06 PM
Last modification on : Monday, April 26, 2021 - 6:14:02 PM
Long-term archiving on: : Thursday, June 13, 2019 - 3:15:28 PM
File
Nucleic Acids Research, 2017.p...
Publication funded by an institution
Licence
Distributed under a Creative Commons Attribution 4.0 International License