Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death.

Human APOBEC3 enzymes deaminate single stranded DNA. At least five can deaminate mitochondrial DNA in the cytoplasm, while three can deaminate viral DNA in the nucleus. However, only one, APOBEC3A, can hypermutate genomic DNA. We analysed the distribution and function of the two APOBEC3A isoforms p1...

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Autores principales:	Bianka Mussil, Rodolphe Suspène, Marie-Ming Aynaud, Anne Gauvrit, Jean-Pierre Vartanian, Simon Wain-Hobson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/644e6451a7ab47d391e496f32021d022
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spelling	oai:doaj.org-article:644e6451a7ab47d391e496f32021d0222021-11-18T08:58:42ZHuman APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death.1932-620310.1371/journal.pone.0073641https://doaj.org/article/644e6451a7ab47d391e496f32021d0222013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23977391/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Human APOBEC3 enzymes deaminate single stranded DNA. At least five can deaminate mitochondrial DNA in the cytoplasm, while three can deaminate viral DNA in the nucleus. However, only one, APOBEC3A, can hypermutate genomic DNA. We analysed the distribution and function of the two APOBEC3A isoforms p1 and p2 in transfected cell lines. Both can translocate to the nucleus and hypermutate CMYC DNA and induce DNA double strand breaks as visualized by the detection of ©H2AX or Chk2. APOBEC3A induced G1 phase cell cycle arrest and triggered several members of the intrinsic apoptosis pathway. Activation of purified human CD4+ T lymphocytes with PHA, IL2 and interferon α resulted in C->T hypermutation of genomic DNA and double stranded breaks suggesting a role for APOBEC3A in pro-inflammatory conditions. As chronic inflammation underlies many diseases including numerous cancers, it is possible that APOBEC3A induction may generate many of the lesions typical of a cancer genome.Bianka MussilRodolphe SuspèneMarie-Ming AynaudAnne GauvritJean-Pierre VartanianSimon Wain-HobsonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e73641 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bianka Mussil Rodolphe Suspène Marie-Ming Aynaud Anne Gauvrit Jean-Pierre Vartanian Simon Wain-Hobson Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death.
description	Human APOBEC3 enzymes deaminate single stranded DNA. At least five can deaminate mitochondrial DNA in the cytoplasm, while three can deaminate viral DNA in the nucleus. However, only one, APOBEC3A, can hypermutate genomic DNA. We analysed the distribution and function of the two APOBEC3A isoforms p1 and p2 in transfected cell lines. Both can translocate to the nucleus and hypermutate CMYC DNA and induce DNA double strand breaks as visualized by the detection of ©H2AX or Chk2. APOBEC3A induced G1 phase cell cycle arrest and triggered several members of the intrinsic apoptosis pathway. Activation of purified human CD4+ T lymphocytes with PHA, IL2 and interferon α resulted in C->T hypermutation of genomic DNA and double stranded breaks suggesting a role for APOBEC3A in pro-inflammatory conditions. As chronic inflammation underlies many diseases including numerous cancers, it is possible that APOBEC3A induction may generate many of the lesions typical of a cancer genome.
format	article
author	Bianka Mussil Rodolphe Suspène Marie-Ming Aynaud Anne Gauvrit Jean-Pierre Vartanian Simon Wain-Hobson
author_facet	Bianka Mussil Rodolphe Suspène Marie-Ming Aynaud Anne Gauvrit Jean-Pierre Vartanian Simon Wain-Hobson
author_sort	Bianka Mussil
title	Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death.
title_short	Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death.
title_full	Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death.
title_fullStr	Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death.
title_full_unstemmed	Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death.
title_sort	human apobec3a isoforms translocate to the nucleus and induce dna double strand breaks leading to cell stress and death.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/644e6451a7ab47d391e496f32021d022
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Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death.

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