Alternative titles; symbolsTEN1, S. POMBE, HOMOLOG OFCHROMOSOME 17 OPEN READING FRAME 106; C17ORF106HGNC Approved Gene Symbol: TEN1Cytogenetic location: 17q25.1 ...
Alternative titles; symbols
HGNC Approved Gene Symbol: TEN1
Cytogenetic location: 17q25.1 Genomic coordinates (GRCh38): 17:75,979,239-76,000,585 (from NCBI)
TEN1 appears to function in a telomere-associated complex with STN1 (613128) and CTC1 (613129) (Miyake et al., 2009).
▼ Cloning and Expression
By RT-PCR of HeLa cell mRNA, Miyake et al. (2009) cloned C17ORF106, which they called TEN1 based on its homology with yeast Ten1. The deduced 122-amino acid protein is made up primarily of an oligonucleotide/oligosaccharide-binding (OB) fold domain that is predicted to bind single-stranded DNA (ssDNA). Immunohistochemical analysis and FISH revealed that TEN1 colocalized with telomeric DNA.
▼ Gene Function
Using Western blot analysis of coimmunoprecipitated proteins and yeast 2-hybrid assays, Miyake et al. (2009) showed that TEN1 interacted with STN1 and CTC1 in a complex, which the authors called the CST complex. STN1 interacted with both CTC1 and TEN1, but CTC1 and TEN1 did not show significant interaction. The CST complex immunoprecipitated telomeric DNA, but not Alu repeat DNA, from HeLa cells. Only a fraction of telomeres associated with the CST complex, and association of the CST complex with telomeres did not vary during the cell cycle. The CST complex, but not its individual components, bound ssDNA with high affinity and in a sequence-independent manner. The CST complex appeared to protect telomeres independently of POT1 (606478). Knockdown studies suggested that the CST complex and POT1 play redundant roles in telomere protection.
Chen et al. (2012) demonstrated that the human CST complex, implicated in telomere protection and DNA metabolism, inhibits telomerase (see 602322) activity through primer sequestration and physical interaction with the POT1-TPP1 (609377) telomerase processivity factor. CST competes with POT1-TPP1 for telomeric DNA, and CST-telomeric-DNA binding increases during late S/G2 phase only on telomerase action, coinciding with telomerase shut-off. Depletion of CST allows excessive telomerase activity, promoting telomere elongation. Chen et al. (2012) proposed that through binding of the telomerase-extended telomere, CST limits telomerase action at individual telomeres to approximately one binding and extension event per cell cycle. The authors suggested that their findings defined the sequence of events that occur to first enable and then terminate telomerase-mediated telomere elongation.
Hartz (2009) mapped the TEN1 gene to chromosome 17q25.1 based on an alignment of the TEN1 sequence (GenBank AK097104) with the genomic sequence (GRCh37).
▼ Biochemical Features
The CTC1 (613129)-STN1 (613128)-TEN1 complex, also known as the CST complex, is essential for telomere maintenance and resolution of stalled replication forks genomewide. Lim et al. (2020) reported the 3.0-angstrom cryoelectron microscopy structure of human CST bound to telomeric single-stranded DNA, which assembles as a decameric supercomplex. The atomic model of the 134-kD CTC1 subunit, built almost entirely de novo, revealed the overall architecture of CST and the DNA-binding anchor site. The carboxyl-terminal domain of STN1 interacts with CTC1 at 2 separate docking sites, allowing allosteric mediation of CST decamer assembly. Furthermore, ssDNA appears to staple 2 monomers to nucleate decamer assembly. CTC1 has stronger structural similarity to replication protein A (RPA; see 179835) than the expected similarity to yeast Cdc13. The decameric structure suggested that CST can organize ssDNA analogously to the nucleosome's organization of double-stranded DNA.