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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| Format: | Article |
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Nature Portfolio
2018-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-23690-y |
| _version_ | 1818344021787934720 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T16:39:51Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T16:39:51Z |
| publishDate | 2018-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-ad38501bd0364dfbada911fe5c79d8992022-12-21T23:38:18ZengNature PortfolioScientific Reports2045-23222018-03-01811910.1038/s41598-018-23690-yThe mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repairFenna Hensen0Amandine Moretton1Selma van Esveld2Géraldine Farge3Johannes N. Spelbrink4Radboud Center for Mitochondrial Medicine, Department of PaediatricsUniversité Clermont Auvergne, CNRS/IN2P3, Laboratoire de Physique de Clermont, BP 10448Radboud Center for Mitochondrial Medicine & Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life SciencesUniversité Clermont Auvergne, CNRS/IN2P3, Laboratoire de Physique de Clermont, BP 10448Radboud Center for Mitochondrial Medicine, Department of PaediatricsAbstract 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.https://doi.org/10.1038/s41598-018-23690-y |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-018-23690-y |
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