Omics · study · 2026
Impaired synthesis of both telomere strands and adaptive TERT reduction in RTEL1 ATPase-dead cells
Listed in NCBI GEO
Regulator of Telomere Elongation Helicase 1 (RTEL1) plays a critical role in telomere replication by disassembling DNA secondary structures such as G-quadruplexes and telomeric loops (T-loops).
Description
However, its precise mechanism remains unclear. Previously, we generated HeLa cells homozygous for ATPase-dead RTEL1.
Here, we found that these cells have a 50-60% reduction in the synthesis of both telomere strands, indicating that RTEL1 ATPase activity is essential for replicating both leading and lagging telomeric DNA. Surprisingly, these cells also showed a substantial reduction in Telomerase Reverse Transcriptase (TERT) mRNA levels and a 60-80% reduction in telomerase activity, without activating alternative lengthening of telomeres (ALT).
Read the rest (1 more)
Forced TERT overexpression suppressed proliferation and caused late S/G2 accumulation, implying that the natural TERT reduction provides adaptive resistance. Expressing wild-type (WT) RTEL1 at levels close to physiological levels failed to rescue growth defects, suggesting a dominant-negative effect. These results reveal unexpected interactions between RTEL1 and telomerase and show how cancer cells compensate for RTEL1 dysfunction by decreasing TERT expression.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338949 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338949 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1496430 ncbi.nlm.nih.gov/bioproject/PRJNA1496430 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE338949 | 14 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].anzsrc:group:3105 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (70%) |
| 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 |