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...
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Autor*in:	Fenna Hensen [verfasserIn] Amandine Moretton [verfasserIn] Selma van Esveld [verfasserIn] Géraldine Farge [verfasserIn] Johannes N. Spelbrink [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Übergeordnetes Werk:	In: Scientific Reports - Nature Portfolio, 2011, 8(2018), 1, Seite 9
Übergeordnetes Werk:	volume:8 ; year:2018 ; number:1 ; pages:9

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41598-018-23690-y

Katalog-ID:	DOAJ048374334

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allfields	10.1038/s41598-018-23690-y doi (DE-627)DOAJ048374334 (DE-599)DOAJad38501bd0364dfbada911fe5c79d899 DE-627 ger DE-627 rakwb eng Fenna Hensen verfasserin aut The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Amandine Moretton verfasserin aut Selma van Esveld verfasserin aut Géraldine Farge verfasserin aut Johannes N. Spelbrink verfasserin aut In Scientific Reports Nature Portfolio, 2011 8(2018), 1, Seite 9 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:8 year:2018 number:1 pages:9 https://doi.org/10.1038/s41598-018-23690-y kostenfrei https://doaj.org/article/ad38501bd0364dfbada911fe5c79d899 kostenfrei https://doi.org/10.1038/s41598-018-23690-y kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2018 1 9
spelling	10.1038/s41598-018-23690-y doi (DE-627)DOAJ048374334 (DE-599)DOAJad38501bd0364dfbada911fe5c79d899 DE-627 ger DE-627 rakwb eng Fenna Hensen verfasserin aut The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Amandine Moretton verfasserin aut Selma van Esveld verfasserin aut Géraldine Farge verfasserin aut Johannes N. Spelbrink verfasserin aut In Scientific Reports Nature Portfolio, 2011 8(2018), 1, Seite 9 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:8 year:2018 number:1 pages:9 https://doi.org/10.1038/s41598-018-23690-y kostenfrei https://doaj.org/article/ad38501bd0364dfbada911fe5c79d899 kostenfrei https://doi.org/10.1038/s41598-018-23690-y kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2018 1 9
allfields_unstemmed	10.1038/s41598-018-23690-y doi (DE-627)DOAJ048374334 (DE-599)DOAJad38501bd0364dfbada911fe5c79d899 DE-627 ger DE-627 rakwb eng Fenna Hensen verfasserin aut The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Amandine Moretton verfasserin aut Selma van Esveld verfasserin aut Géraldine Farge verfasserin aut Johannes N. Spelbrink verfasserin aut In Scientific Reports Nature Portfolio, 2011 8(2018), 1, Seite 9 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:8 year:2018 number:1 pages:9 https://doi.org/10.1038/s41598-018-23690-y kostenfrei https://doaj.org/article/ad38501bd0364dfbada911fe5c79d899 kostenfrei https://doi.org/10.1038/s41598-018-23690-y kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2018 1 9
allfieldsGer	10.1038/s41598-018-23690-y doi (DE-627)DOAJ048374334 (DE-599)DOAJad38501bd0364dfbada911fe5c79d899 DE-627 ger DE-627 rakwb eng Fenna Hensen verfasserin aut The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Amandine Moretton verfasserin aut Selma van Esveld verfasserin aut Géraldine Farge verfasserin aut Johannes N. Spelbrink verfasserin aut In Scientific Reports Nature Portfolio, 2011 8(2018), 1, Seite 9 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:8 year:2018 number:1 pages:9 https://doi.org/10.1038/s41598-018-23690-y kostenfrei https://doaj.org/article/ad38501bd0364dfbada911fe5c79d899 kostenfrei https://doi.org/10.1038/s41598-018-23690-y kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2018 1 9
allfieldsSound	10.1038/s41598-018-23690-y doi (DE-627)DOAJ048374334 (DE-599)DOAJad38501bd0364dfbada911fe5c79d899 DE-627 ger DE-627 rakwb eng Fenna Hensen verfasserin aut The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Amandine Moretton verfasserin aut Selma van Esveld verfasserin aut Géraldine Farge verfasserin aut Johannes N. Spelbrink verfasserin aut In Scientific Reports Nature Portfolio, 2011 8(2018), 1, Seite 9 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:8 year:2018 number:1 pages:9 https://doi.org/10.1038/s41598-018-23690-y kostenfrei https://doaj.org/article/ad38501bd0364dfbada911fe5c79d899 kostenfrei https://doi.org/10.1038/s41598-018-23690-y kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2018 1 9
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source	In Scientific Reports 8(2018), 1, Seite 9 volume:8 year:2018 number:1 pages:9
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topic_title	The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair
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title	The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair
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title_sort	mitochondrial outer-membrane location of the exd2 exonuclease contradicts its direct role in nuclear dna repair
title_auth	The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair
abstract	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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair
url	https://doi.org/10.1038/s41598-018-23690-y https://doaj.org/article/ad38501bd0364dfbada911fe5c79d899 https://doaj.org/toc/2045-2322
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The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair

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