Omics · study · 2026
DNA-PK Mediated CRTC2 Phosphorylation Promotes CRTC2 Relocation from Transcription to Repair Complexes Enhancing NHEJ and Suppressing Abscopal Effect [CUT&Tag]
Listed in NCBI GEO
DNA damage repair and transcription are antagonistic cellular processes that require precise spatiotemporal coordination to maintain genomic integrity.
Description
Transcriptional silencing at DSB sites is essential for efficient repair, mediated through localized histone modifications and direct inhibition of RNA polymerase II (Pol II). However, the role of transcriptional activators in coordinating DSB repair with transcriptional silencing remains elusive.
Here, we identify the transcriptional coactivator CRTC2 as a key coordinator of DNA repair and transcriptional regulation. We demonstrate that CRTC2 promotes canonical non-homologous end joining (c-NHEJ) both in vitro and in vivo. Mechanistically, PARP1 activation recruits CRTC2 to DNA breaks, where it facilitates DNA-PKcs recruitment and assembly of the DNA-PK holoenzyme, thereby driving c-NHEJ.
Read the rest (2 more)
DNA-PK–mediated phosphorylation of CRTC2 at Ser433 dissociates it from transcriptional complexes, suppressing target gene transcription, and promoting its incorporation into DNA repair complexes. Thus, establishing a positive feedback loop that enhances NHEJ efficiency. CRTC2 loss radiosensitizes cancer cells, potentiates irradiation-induced cGAS–STING activation, promotes cytotoxic CD8⁺ T cell infiltration, and enhances the abscopal effect.
Furthermore, AAV8-mediated targeting of CRTC2 sensitizes tumors to radioimmunotherapy. Our results reveal CRTC2 as bifunctional nodal effector coupling transcriptional silencing to DNA repair and propose its inhibition as a promising strategy for radioimmunotherapy sensitization in resistant malignancies.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306488 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306488 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1310967 ncbi.nlm.nih.gov/bioproject/PRJNA1310967 ↗
project · from NCBI GEO
- PubMed 42151152 pubmed.ncbi.nlm.nih.gov/42151152 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE306488 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |