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The 19S proteasome subunit Rpn7 stabilizes DNA damage foci upon genotoxic insult

Lookup NU author(s): Avgi Tsolou, Dr Glyn Nelson, Dr Gabriele Saretzki, Professor Thomas von Zglinicki

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Abstract

The DNA damage response (DDR) orchestrates the recruitment of repair proteins at sites of damage and arrests cell-cycle progression until completion of repair. Upon irreparable damage, DNA damage foci persist (long-lived foci) and this is believed to induce cellular senescence. The resolution of DNA damage foci has previously been shown to depend on proteasomal degradation and various proteasome subunits have been implicated in the DDR. In this study, we aimed to analyze the possible distinct roles of individual proteasome subunits in the DDR. We show that specific 19S subunits respond to DNA damage by increased protein levels and nuclear translocation. Importantly, two 19S subunits, Rpn7 and Rpn11, colocalize with DNA damage foci over their whole lifespan. Although silencing of Rpn11 does not affect foci stability and lifespan, silencing of Rpn7 promotes faster resolution of DNA damage foci following genotoxic insult. For the first time, we provide evidence that Rpn7 silencing specifically decreases the frequencies of long-lived DNA damage foci without, however, affecting the repair rate of short-lived foci. Therefore, we propose that interaction of Rpn7 with DDR foci in situ mediates the protection of DNA damage foci from premature resolution. We suggest that this interaction is involved in enabling cellular senescence following genotoxic insult. 2012 IUBMB IUBMB Life, 2012


Publication metadata

Author(s): Tsolou A; Saretzki G; Nelson G; von Zglinicki T; Trachana V; Chondrogianni N; Gonos ES

Publication type: Article

Publication status: Published

Journal: IUBMB Life

Year: 2012

Volume: 64

Issue: 5

Pages: 432-442

Print publication date: 31/03/2012

ISSN (print): 1521-6543

ISSN (electronic): 1521-6551

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1002/iub.1018

DOI: 10.1002/iub.1018


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