The nuclear oncogene SET controls DNA repair by KAP1 and HP1 retention to chromatin

Kalousi, Alkmini, Hoffbeck, Anne-Sophie, Selemenakis, Platonas N, Pinder, Jordan, Savage, Kienan I, Khanna, Kum Kum, Brino, Laurent, Dellaire, Graham, Gorgoulis, Vassilis G and Soutoglou, Evi (2015) The nuclear oncogene SET controls DNA repair by KAP1 and HP1 retention to chromatin. Cell Reports, 11 (1). pp. 149-163. ISSN 2211-1247

[img] PDF - Published Version
Available under License Creative Commons Attribution-NonCommercial No Derivatives.

Download (8MB)

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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 06 Jul 2020 09:44
Last Modified: 02 Mar 2021 10:38
URI: http://sro.sussex.ac.uk/id/eprint/92312

View download statistics for this item

📧 Request an update