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Elephant APOBEC3A cytidine deaminase induces massive double-stranded DNA breaks and apoptosis
The incidence of developing cancer should increase with the body mass, yet is not the case, a conundrum referred to as Peto’s paradox. Elephants have a lower incidence of cancer suggesting that these animals have probably evolved different ways to protect themselves against the disease. The paradox...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345769/ https://www.ncbi.nlm.nih.gov/pubmed/30679716 http://dx.doi.org/10.1038/s41598-018-37305-z |
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author | Li, Xiongxiong Caval, Vincent Wain-Hobson, Simon Vartanian, Jean-Pierre |
author_facet | Li, Xiongxiong Caval, Vincent Wain-Hobson, Simon Vartanian, Jean-Pierre |
author_sort | Li, Xiongxiong |
collection | PubMed |
description | The incidence of developing cancer should increase with the body mass, yet is not the case, a conundrum referred to as Peto’s paradox. Elephants have a lower incidence of cancer suggesting that these animals have probably evolved different ways to protect themselves against the disease. The paradox is worth revisiting with the realization that most mammals encode an endogenous APOBEC3 cytidine deaminase capable of mutating single stranded DNA. Indeed, the mutagenic activity of some APOBEC3 enzymes has been shown to introduce somatic mutations into genomic DNA. These enzymes are now recognized as causal agent responsible for the accumulation of CG- > TA transitions and DNA breaks leading to chromosomal rearrangements in human cancer genomes. Here, we identified an elephant A3Z1 gene, related to human APOBEC3A and showed that it could efficiently deaminate cytidine, 5-methylcytidine and produce DNA breaks leading to massive apoptosis, similar to other mammalian APOBEC3A enzymes where body mass varies by up to four orders of magnitude. Consequently, it could be considered that eAZ1 might contribute to cancer in elephants in a manner similar to their proposed role in humans. If so, eAZ1 might be particularly well regulated to counter Peto’s paradox. |
format | Online Article Text |
id | pubmed-6345769 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63457692019-01-28 Elephant APOBEC3A cytidine deaminase induces massive double-stranded DNA breaks and apoptosis Li, Xiongxiong Caval, Vincent Wain-Hobson, Simon Vartanian, Jean-Pierre Sci Rep Article The incidence of developing cancer should increase with the body mass, yet is not the case, a conundrum referred to as Peto’s paradox. Elephants have a lower incidence of cancer suggesting that these animals have probably evolved different ways to protect themselves against the disease. The paradox is worth revisiting with the realization that most mammals encode an endogenous APOBEC3 cytidine deaminase capable of mutating single stranded DNA. Indeed, the mutagenic activity of some APOBEC3 enzymes has been shown to introduce somatic mutations into genomic DNA. These enzymes are now recognized as causal agent responsible for the accumulation of CG- > TA transitions and DNA breaks leading to chromosomal rearrangements in human cancer genomes. Here, we identified an elephant A3Z1 gene, related to human APOBEC3A and showed that it could efficiently deaminate cytidine, 5-methylcytidine and produce DNA breaks leading to massive apoptosis, similar to other mammalian APOBEC3A enzymes where body mass varies by up to four orders of magnitude. Consequently, it could be considered that eAZ1 might contribute to cancer in elephants in a manner similar to their proposed role in humans. If so, eAZ1 might be particularly well regulated to counter Peto’s paradox. Nature Publishing Group UK 2019-01-24 /pmc/articles/PMC6345769/ /pubmed/30679716 http://dx.doi.org/10.1038/s41598-018-37305-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Li, Xiongxiong Caval, Vincent Wain-Hobson, Simon Vartanian, Jean-Pierre Elephant APOBEC3A cytidine deaminase induces massive double-stranded DNA breaks and apoptosis |
title | Elephant APOBEC3A cytidine deaminase induces massive double-stranded DNA breaks and apoptosis |
title_full | Elephant APOBEC3A cytidine deaminase induces massive double-stranded DNA breaks and apoptosis |
title_fullStr | Elephant APOBEC3A cytidine deaminase induces massive double-stranded DNA breaks and apoptosis |
title_full_unstemmed | Elephant APOBEC3A cytidine deaminase induces massive double-stranded DNA breaks and apoptosis |
title_short | Elephant APOBEC3A cytidine deaminase induces massive double-stranded DNA breaks and apoptosis |
title_sort | elephant apobec3a cytidine deaminase induces massive double-stranded dna breaks and apoptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345769/ https://www.ncbi.nlm.nih.gov/pubmed/30679716 http://dx.doi.org/10.1038/s41598-018-37305-z |
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