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Series GSE218238 Query DataSets for GSE218238
Status Public on Aug 01, 2023
Title RNAPII-dependent ATM signaling at collisions with replication forks [CUT&RUN]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII promotes activation of the ATM kinase at TRCs to drive DNA repair. We show the ATPase Wrnip1 that binds and protects stalled replication forks, associates with RNAPII and limits ATM activation. Wrnip1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase Huwe1. Mutation of Huwe1 promotes the transfer of Wrnip1 onto replisome and induces TRCs stimulating ATM activation on RNAPII. This mechanism is evoked early upon replicative stress to induce Wrnip1 translocation and ATM signaling at TRCs. Thus, although primarily considered as genotoxic events, TRCs can provide a mechanism to maintain genome stability under replicative stress.
 
Overall design CUT&RUN experiment using a WRNIP1 antibody in HUWE1-WT (WT) and HUWE1-CS (CS) cells.
 
Contributor(s) Einig E, Popov N
Citation(s) 37620345
Submission date Nov 17, 2022
Last update date Aug 25, 2023
Contact name Elias Einig
Organization name University Hospital Tübingen
Department Medical Oncology and Pulmonology
Lab Nikita Popov
Street address Otfried-Müller Straße 14
City Tübingen
ZIP/Postal code 72076
Country Germany
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (6)
GSM6737715 HCT116, HUWE1-WT, input for Cut&Run
GSM6737716 HCT116, HUWE1-CS, input for Cut&Run
GSM6737717 HCT116, HUWE1-WT, WRNIP1 Cut&Run, rep1
This SubSeries is part of SuperSeries:
GSE218240 RNAPII-dependent ATM signaling at collisions with replication forks
Relations
BioProject PRJNA902791

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE218238_RAW.tar 104.2 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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