SQSTM1/p62 mediates crosstalk between autophagy and the UPS in DNA repair

Graeme Hewitt, Bernadette Carroll, Rezazadeh Sarallah, Clara Correia-Melo, Mikołaj Ogrodnik, Glyn Nelson, Elsje G. Otten, Diego Manni, Robin Antrobus, Brian A. Morgan, Thomas von Zglinicki, Diana Jurk, Andrei Seluanov, Vera Gorbunova, Terje Johansen, João F. Passos*, Viktor I. Korolchuk

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

109 Citations (Scopus)
360 Downloads (Pure)


SQSTM1/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-span-extending dietary restriction, suggesting that an imbalance in the mechanism identified here may contribute to aging and age-related diseases.

Original languageEnglish
Pages (from-to)1917-1930
Number of pages14
Issue number10
Early online date23 Aug 2016
Publication statusPublished - 2 Oct 2016


  • aging
  • autophagy
  • DNA damage
  • homologous recombination
  • nonhomologous end joining
  • SQSTM1


Dive into the research topics of 'SQSTM1/p62 mediates crosstalk between autophagy and the UPS in DNA repair'. Together they form a unique fingerprint.

Cite this