Research Article

The structure of human CST reveals a decameric assembly bound to telomeric DNA

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Science  05 Jun 2020:
Vol. 368, Issue 6495, pp. 1081-1085
DOI: 10.1126/science.aaz9649

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Architecture of DNA-organizing complex

The highly conserved mammalian CTC1-STN1-TEN1 (CST) complex is critical for genome stability and telomere maintenance. Lim et al. solved the structure of the human CST complex using cryo–electron microscopy. CST forms an unprecedented and substantial decameric supercomplex triggered by telomeric single-stranded binding. This decameric form with single-stranded DNA–binding capacity of up to 10 telomeric repeats, suggested the possibility of CST organizing telomere overhangs into compact and restrictive structures in a manner similar to the nucleosome's organization of double-stranded DNA. This work provides a platform for understanding the mechanisms of various CST functions.

Science, this issue p. 1081

Abstract

The CTC1-STN1-TEN1 (CST) complex is essential for telomere maintenance and resolution of stalled replication forks genome-wide. Here, we report the 3.0-angstrom cryo–electron microscopy structure of human CST bound to telomeric single-stranded DNA (ssDNA), which assembles as a decameric supercomplex. The atomic model of the 134-kilodalton CTC1 subunit, built almost entirely de novo, reveals the overall architecture of CST and the DNA-binding anchor site. The carboxyl-terminal domain of STN1 interacts with CTC1 at two separate docking sites, allowing allosteric mediation of CST decamer assembly. Furthermore, ssDNA appears to staple two monomers to nucleate decamer assembly. CTC1 has stronger structural similarity to Replication Protein A than the expected similarity to yeast Cdc13. The decameric structure suggests that CST can organize ssDNA analogously to the nucleosome’s organization of double-stranded DNA.

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