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dc.contributor.authorHewitt, Graeme
dc.contributor.authorCarroll, Bernadette
dc.contributor.authorSarallah, Rezazadeh
dc.contributor.authorCorreia-Melo, Clara
dc.contributor.authorOgrodnik, Mikolaj
dc.contributor.authorNelson, Glyn
dc.contributor.authorOtten, Elsje G
dc.contributor.authorManni, Diego
dc.contributor.authorAntrobus, Robin
dc.contributor.authorMorgan, Brian A
dc.contributor.authorvon Zglinicki, Thomas
dc.contributor.authorJurk, Diana
dc.contributor.authorSeluanov, Andrei
dc.contributor.authorGorbunova, Vera
dc.contributor.authorJohansen, Terje
dc.contributor.authorPassos, João F
dc.contributor.authorKorolchuk, Viktor I
dc.date.accessioned2022-04-27T06:34:24Z
dc.date.available2022-04-27T06:34:24Z
dc.date.issued2016-08-23
dc.description.abstractSQSTM1/p62 (sequestosome 1) selectively targets polyubiquitinated proteins for degradation via macroautophagy and the proteasome. Additionally, SQSTM1 shuttles between the cytoplasmic and nuclear compartments, although its role in the nucleus is relatively unknown. Here, we report that SQSTM1 dynamically associates with DNA damage foci (DDF) and regulates DNA repair. Upon induction of DNA damage SQSTM1 interacts with FLNA (filamin A), which has previously been shown to recruit DNA repair protein RAD51 (RAD51 recombinase) to double-strand breaks and facilitate homologous recombination (HR). SQSTM1 promotes proteasomal degradation of FLNA and RAD51 within the nucleus, resulting in reduced levels of nuclear RAD51 and slower DNA repair. SQSTM1 regulates the ratio between HR and nonhomologous end joining (NHEJ) by promoting the latter at the expense of the former. This SQSTM1- dependent mechanism mediates the effect of macroautophagy on DNA repair. Moreover, nuclear localization of SQSTM1 and its association with DDF increase with aging and are prevented by life-spanextending dietary restriction, suggesting that an imbalance in the mechanism identified here may contribute to aging and age-related diseases.en_US
dc.identifier.citationHewitt, Carroll B, Sarallah, Correia-Melo, Ogrodnik, Nelson, Otten, Manni, Antrobus, Morgan, von Zglinicki, Jurk, Seluanov, Gorbunova, Johansen T, Passos, Korolchuk. SQSTM1/p62 mediates crosstalk between autophagy and the UPS in DNA repair. Autophagy. 2016;12(10):1917-1930en_US
dc.identifier.cristinIDFRIDAID 1422262
dc.identifier.doi10.1080/15548627.2016.1210368
dc.identifier.issn1554-8627
dc.identifier.issn1554-8635
dc.identifier.urihttps://hdl.handle.net/10037/24895
dc.language.isoengen_US
dc.publisherTaylor & Francisen_US
dc.relation.journalAutophagy
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2016 The Author(s)en_US
dc.titleSQSTM1/p62 mediates crosstalk between autophagy and the UPS in DNA repairen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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