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GEO help: Mouse over screen elements for information. |
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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
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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.
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Overall design |
CUT&RUN experiment using a WRNIP1 antibody in HUWE1-WT (WT) and HUWE1-CS (CS) cells.
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Contributor(s) |
Einig E, Popov N |
Citation(s) |
37620345 |
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Submission date |
Nov 17, 2022 |
Last update date |
Aug 25, 2023 |
Contact name |
Elias Einig |
Organization name |
University Hospital Tübingen
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Department |
Medical Oncology and Pulmonology
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Lab |
Nikita Popov
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Street address |
Otfried-Müller Straße 14
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City |
Tübingen |
ZIP/Postal code |
72076 |
Country |
Germany |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE218240 |
RNAPII-dependent ATM signaling at collisions with replication forks |
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Relations |
BioProject |
PRJNA902791 |
Supplementary file |
Size |
Download |
File type/resource |
GSE218238_RAW.tar |
104.2 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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