Omics · study · 2026
CHK2 deficiency affects the engagement of DSBs repair pathways following DNA damage
Listed in NCBI GEO
Checkpoint kinase 2 (CHK2) participates in the DNA damage response (DDR) by regulating the cell cycle or inducing apoptosis, and its abnormal activity can lead to cancer development.
Description
CHK2 loss-of-function mutations correlate with the onset of many types of tumors and with therapy resistance. As the exact molecular mechanisms underlying these phenomena are not fully elucidated, we aimed to understand how CHK2 deficiency in cancer cells affects their DDR functionality and their DNA repair ability post-treatment.
Despite compromised RAD51 foci formation, we found that CHK2-deficient HCT116 cancer cells exhibit higher homologous recombination repair (HRR) frequency than CHK2-proficient cells. Transcriptomics analysis revealed a significantly decreased expression of DNA-PKcs and increased NBS1 mRNA levels in CHK2 KO cells compared to their isogenic CHK2 WT line. These changes were also confirmed on a protein level.
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Consequently, the repression of the NHEJ pathway by the DNA-PKcs small molecule inhibitor peposertib further decreased the viability of HCT116 CHK2-proficient cells compared to ionizing radiation alone, while the blockage of HRR by the RAD51 inhibitor CAM833 did not radiosensitize cancer cell lines with distinct CHK2 alterations. In conclusion, our results indicate that CHK2 KO influence DNA repair pathways engagement, and the targeting of these pathways in combination with irradiation deserves further studies to uncover the significance of CHK2 alterations in shaping radiation response.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE303nnn/GSE303774 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303774 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1297661 ncbi.nlm.nih.gov/bioproject/PRJNA1297661 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression 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 | GSE303774 | 15 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:expression-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 |