Summary information and primary citation

PDB-id
8sh0; SNAP-derived features in text and JSON formats; DNAproDB
Class
DNA binding protein-DNA
Method
X-ray (2.16 Å)
Summary
Structure of human pot1 DNA binding domain bound to a 5'-phosphorylated junction of a telomeric DNA hairpin with a 3'-overhang
Reference
Tesmer VM, Brenner KA, Nandakumar J (2023): "Human POT1 protects the telomeric ds-ss DNA junction by capping the 5' end of the chromosome." Science, 381, 771-778. doi: 10.1126/science.adi2436.
Abstract
Protection of telomeres 1 (POT1) is the 3' single-stranded overhang-binding telomeric protein that prevents an ataxia telangiectasia and Rad3-related (ATR) DNA damage response (DDR) at chromosome ends. What precludes the DDR machinery from accessing the telomeric double-stranded-single-stranded junction is unknown. We demonstrate that human POT1 binds this junction by recognizing the phosphorylated 5' end of the chromosome. High-resolution crystallographic structures reveal that the junction is capped by POT1 through a "POT-hole" surface, the mutation of which compromises junction protection in vitro and telomeric 5'-end definition and DDR suppression in human cells. Whereas both mouse POT1 paralogs bind the single-stranded overhang, POT1a, not POT1b, contains a POT-hole and binds the junction, which explains POT1a's sufficiency for end protection. Our study shifts the paradigm for DDR suppression at telomeres by highlighting the importance of protecting the double-stranded-single-stranded junction.

Cartoon-block schematics in six views (download the tarball)

PyMOL session file Download PDB file View in 3Dmol.js