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Series GSE84986 Query DataSets for GSE84986
Status Public on Aug 18, 2016
Title 53BP1 integrates DNA repair and p53-dependent cell fate decisions via distinct mechanisms
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The tumor suppressor protein 53BP1, a pivotal regulator of DNA double-strand break (DSB) repair, was first identified as a p53-interacting protein over two decades ago, however its direct contributions to p53-dependent cellular activities remain undefined. Here, we reveal 53BP1 stimulates genome-wide p53-dependent gene transactivation and repression events in response to ionizing radiation (IR) and synthetic p53 activation. 53BP1-dependent p53 modulation requires both auto-oligomerization and tandem-BRCT domain mediated bivalent interactions with p53 and the ubiquitin-specific protease USP28. Loss of these activities results in inefficient p53-dependent cell-cycle checkpoint and exit responses. Furthermore, we demonstrate 53BP1-USP28 cooperation to be essential for normal p53-promoter element interactions and gene transactivation-associated events, yet dispensable for 53BP1-dependent DSB repair regulation. Collectively, our data provides a mechanistic explanation for 53BP1-p53 cooperation in controlling anti-tumorigenic cell fate decisions, and reveal these activities to be distinct and separable from 53BP1’s regulation of DNA double-strand break repair pathway choice.
 
Overall design We evaluated the transcriptional profiles of two 53BP1Δ cell lines and included a positive (WT) and a negative (p53Δ) controls. These cell lines were treated with Nutlin-3, ionising radiation or mock treated. Three independent replicates were included for each independent condition generating a total of 36 samples.
 
Contributor(s) Cuella-Martin R, Oliveira C, Lockstone HE, Snellenberg S, Gromulsova N, Chapman JR
Citation(s) 27546791
Submission date Jul 29, 2016
Last update date May 15, 2019
Contact name Jonathan Ross Chapman
E-mail(s) rchapman@well.ox.ac.uk
Organization name Wellcome Trust Centre for Human Genetics
Department Nuffield Department of Medicine (University of Oxford)
Street address Roosevelt Drive
City Oxford
ZIP/Postal code OX3 7BN
Country United Kingdom
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (36)
GSM2255508 Wild-type untreated replicate 1
GSM2255509 Wild-type IR replicate 1
GSM2255510 Wild-type Nutlin-3 replicate 1
Relations
BioProject PRJNA335834
SRA SRP080321

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE84986_RAW.tar 7.3 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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