Impaired synthesis of both telomere strands and adaptive TERT reduction in RTEL1 ATPase-dead cells

HeLa cells homozygous for ATPase-dead RTEL1 show a 50–77% reduction in synthesis of both telomere strands, indicating RTEL1 ATPase activity supports leading- and lagging-strand telomere replication.

• Why it matters: RTEL1 is known to resolve telomeric DNA structures, but how its ATPase function affects telomere strand synthesis and telomerase regulation is unclear, especially in cancer cells.
• What they did: The study used HeLa cells engineered to be homozygous for ATPase-dead RTEL1, measuring telomere-strand synthesis, TERT mRNA, telomerase activity, ALT status, and testing TERT overexpression and RTEL1 isoform expression.
• The result: ATPase-dead cells had reduced TERT mRNA and ~80% lower telomerase activity without ALT activation; TERT overexpression suppressed proliferation and late S/G2 accumulation, while expressing the longest RTEL1 isoform near physiological levels did not rescue growth defects.

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