The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair

Abstract EXD2 is a recently identified exonuclease that has been implicated in nuclear double-strand break repair. Given our long standing interest in mitochondrial DNA maintenance and indications that EXD2 could also be a mitochondrial protein we sought to determine its cellular localization and po...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Fenna Hensen, Amandine Moretton, Selma van Esveld, Géraldine Farge, Johannes N. Spelbrink
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ad38501bd0364dfbada911fe5c79d899
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ad38501bd0364dfbada911fe5c79d899
record_format	dspace
spelling	oai:doaj.org-article:ad38501bd0364dfbada911fe5c79d8992021-12-02T15:07:58ZThe mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair10.1038/s41598-018-23690-y2045-2322https://doaj.org/article/ad38501bd0364dfbada911fe5c79d8992018-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-23690-yhttps://doaj.org/toc/2045-2322Abstract EXD2 is a recently identified exonuclease that has been implicated in nuclear double-strand break repair. Given our long standing interest in mitochondrial DNA maintenance and indications that EXD2 could also be a mitochondrial protein we sought to determine its cellular localization and possible mitochondrial associated functions. Our results show that EXD2 indeed shows mitochondrial localization, but, surprisingly, is found predominantly associated with the mitochondrial outer-membrane. Gradient purified nuclei show only the faintest hint of EXD2 presence while overexpression of the predicted full-length protein shows exclusive mitochondrial localization. Importantly, induction of double-strand DNA breaks via X-irradiation or Zeocin treatment does not support the notion that EXD2 re-locates to the nucleus following double-strand breaks and thus is unlikely to have a direct role in nuclear DNA repair. Knockdown or overexpression of EXD2 affects the cellular distribution of mitochondria. These results suggest that the reported defects in nuclear DNA repair following EXD2 depletion are likely an indirect consequence of altered mitochondrial dynamics and/or function.Fenna HensenAmandine MorettonSelma van EsveldGéraldine FargeJohannes N. SpelbrinkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fenna Hensen Amandine Moretton Selma van Esveld Géraldine Farge Johannes N. Spelbrink The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair
description	Abstract EXD2 is a recently identified exonuclease that has been implicated in nuclear double-strand break repair. Given our long standing interest in mitochondrial DNA maintenance and indications that EXD2 could also be a mitochondrial protein we sought to determine its cellular localization and possible mitochondrial associated functions. Our results show that EXD2 indeed shows mitochondrial localization, but, surprisingly, is found predominantly associated with the mitochondrial outer-membrane. Gradient purified nuclei show only the faintest hint of EXD2 presence while overexpression of the predicted full-length protein shows exclusive mitochondrial localization. Importantly, induction of double-strand DNA breaks via X-irradiation or Zeocin treatment does not support the notion that EXD2 re-locates to the nucleus following double-strand breaks and thus is unlikely to have a direct role in nuclear DNA repair. Knockdown or overexpression of EXD2 affects the cellular distribution of mitochondria. These results suggest that the reported defects in nuclear DNA repair following EXD2 depletion are likely an indirect consequence of altered mitochondrial dynamics and/or function.
format	article
author	Fenna Hensen Amandine Moretton Selma van Esveld Géraldine Farge Johannes N. Spelbrink
author_facet	Fenna Hensen Amandine Moretton Selma van Esveld Géraldine Farge Johannes N. Spelbrink
author_sort	Fenna Hensen
title	The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair
title_short	The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair
title_full	The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair
title_fullStr	The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair
title_full_unstemmed	The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair
title_sort	mitochondrial outer-membrane location of the exd2 exonuclease contradicts its direct role in nuclear dna repair
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/ad38501bd0364dfbada911fe5c79d899
work_keys_str_mv	AT fennahensen themitochondrialoutermembranelocationoftheexd2exonucleasecontradictsitsdirectroleinnucleardnarepair AT amandinemoretton themitochondrialoutermembranelocationoftheexd2exonucleasecontradictsitsdirectroleinnucleardnarepair AT selmavanesveld themitochondrialoutermembranelocationoftheexd2exonucleasecontradictsitsdirectroleinnucleardnarepair AT geraldinefarge themitochondrialoutermembranelocationoftheexd2exonucleasecontradictsitsdirectroleinnucleardnarepair AT johannesnspelbrink themitochondrialoutermembranelocationoftheexd2exonucleasecontradictsitsdirectroleinnucleardnarepair AT fennahensen mitochondrialoutermembranelocationoftheexd2exonucleasecontradictsitsdirectroleinnucleardnarepair AT amandinemoretton mitochondrialoutermembranelocationoftheexd2exonucleasecontradictsitsdirectroleinnucleardnarepair AT selmavanesveld mitochondrialoutermembranelocationoftheexd2exonucleasecontradictsitsdirectroleinnucleardnarepair AT geraldinefarge mitochondrialoutermembranelocationoftheexd2exonucleasecontradictsitsdirectroleinnucleardnarepair AT johannesnspelbrink mitochondrialoutermembranelocationoftheexd2exonucleasecontradictsitsdirectroleinnucleardnarepair
_version_	1718388339881541632

The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair

Ejemplares similares