Human cancer cells harbor T-stumps, a distinct class of extremely short telomeres.
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.
Xu
Lifeng
L
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143-2200, USA.
Blackburn
Elizabeth H
EH
D017209:Apoptosis / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D016160:Retinoblastoma Protein / Q000378:metabolism; D035182:TATA Box Binding Protein-Like Proteins / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism* / Q000648:ultrastructure; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D035182:TATA Box Binding Protein-Like Proteins; C504753:TERF2 protein, human; C495901:TP53 protein, human; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C509186:TERT protein, human; D019098:Telomerase