Human Cancer Cells Harbor T-Stumps, a Distinct Class of Extremely Short Telomeres

• Published in: Molecular cell Vol. 28; no. 2; pp. 315 - 327
• Main Authors: Xu, Lifeng, Blackburn, Elizabeth H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.10.2007
• Subjects: Apoptosis - genetics; Ataxia Telangiectasia Mutated Proteins; Base Sequence; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Proliferation; Cloning, Molecular; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fibroblasts - enzymology; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Molecular Sequence Data; Neoplasms - enzymology; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Nuclear Proteins - metabolism; Phosphorylation; Polymerase Chain Reaction - methods; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Reproducibility of Results; Retinoblastoma Protein - metabolism; SIGNALING; TATA Box Binding Protein-Like Proteins - metabolism; Telomerase - genetics; Telomerase - metabolism; Telomere - metabolism; Telomere - ultrastructure; Telomeric Repeat Binding Protein 1 - metabolism; Telomeric Repeat Binding Protein 2; Transduction, Genetic; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; SIGNALING
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2007.10.005

Using a modified single telomere length analysis protocol (STELA) to clone and examine the sequence composition of individual human XpYp telomeres, we discovered a distinct class of extremely short telomeres in human cancer cells with active telomerase. We name them “t-stumps,” to distinguish them from the well-regulated longer bulk telomeres. T-stumps contained arrangements of telomeric repeat variants and a minimal run of seven canonical telomeric TTAGGG repeats, but all could bind at least one TRF1 or TRF2 in vitro. The abundance of t-stumps was unaffected by ATM alteration but could be changed by manipulating telomerase catalytic subunit (hTERT) levels in cancer cells. We propose that in the setting of active telomerase and compromised checkpoints characteristic of human cancer cells, t-stumps define the minimal telomeric unit that can still be protected by a TRF1/TRF2-capping complex and, further, that hTERT (or telomerase) may have a role in protecting t-stumps.