Cell reportsKalousi.pdf (8.51 MB)
The nuclear oncogene SET controls DNA repair by KAP1 and HP1 retention to chromatin
journal contribution
posted on 2023-06-07, 07:25 authored by Alkmini Kalousi, Anne-Sophie Hoffbeck, Platonas N Selemenakis, Jordan Pinder, Kienan I Savage, Kum Kum Khanna, Laurent Brino, Graham Dellaire, Vassilis G Gorgoulis, Evi SoutoglouEvi SoutoglouCells 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.
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Publication status
- Published
File Version
- Published version
Journal
Cell ReportsISSN
2211-1247Publisher
ElsevierExternal DOI
Issue
1Volume
11Page range
149-163Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2020-07-06First Open Access (FOA) Date
2020-07-06First Compliant Deposit (FCD) Date
2020-07-06Usage metrics
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