The Nuclear Oncogene SET Controls DNA Repair by KAP1 and HP1 Retention to Chromatin

Alkmini Kalousi, Anne-Sophie Hoffbeck, Platonas N. Selemenakis, Jordan Pinder, Kienan I. Savage, Kum Kum Khanna, Laurent Brino, Graham Dellaire, Vassilis G. Gorgoulis, Evi Soutoglou

Research output: Contribution to journalArticle

48 Citations (Scopus)
345 Downloads (Pure)

Abstract

Cells experience damage from exogenous and endogenous sources that endanger genome stability. Several cellular pathways have evolved to detect DNA damage and mediate its repair. Although many proteins have been implicated in these processes, only recent studies have revealed how they operate in the context of high-ordered chromatin structure. Here, we identify the nuclear oncogene SET (I2PP2A) as a modulator of DNA damage response (DDR) and repair in chromatin surrounding double-strand breaks (DSBs). We demonstrate that depletion of SET increases DDR and survival in the presence of radiomimetic drugs, while overexpression of SET impairs DDR and homologous recombination (HR)-mediated DNA repair. SET interacts with the Kruppel-associated box (KRAB)-associated co-repressor KAP1, and its overexpression results in the sustained retention of KAP1 and Heterochromatin protein 1 (HP1) on chromatin. Our results are consistent with a model in which SET-mediated chromatin compaction triggers an inhibition of DNA end resection and HR.

Original languageEnglish
Pages (from-to)149-163
Number of pages15
JournalCell Reports
Volume11
Issue number1
Early online date26 Mar 2015
DOIs
Publication statusPublished - 07 Apr 2015

Fingerprint Dive into the research topics of 'The Nuclear Oncogene SET Controls DNA Repair by KAP1 and HP1 Retention to Chromatin'. Together they form a unique fingerprint.

  • Cite this

    Kalousi, A., Hoffbeck, A-S., Selemenakis, P. N., Pinder, J., Savage, K. I., Khanna, K. K., Brino, L., Dellaire, G., Gorgoulis, V. G., & Soutoglou, E. (2015). The Nuclear Oncogene SET Controls DNA Repair by KAP1 and HP1 Retention to Chromatin. Cell Reports, 11(1), 149-163. https://doi.org/10.1016/j.celrep.2015.03.005