GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338949/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338949GEOGSEfalseImpaired synthesis of both telomere strands and adaptive TERT reduction in RTEL1 ATPase-dead cellsRegulator 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). 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). 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.2026/07/24GSE338949GSM9885457GSM9885456GSM9885459GSM9885458GSM9885460GSM9885451GSM9885462GSM9885461GSM9885453GSM9885452GSM9885455GSM988545434284338949Homo sapiens