Human POT1 protects the telomeric ds-ss DNA junction by capping the 5' end of the chromosome.
Science
; 381(6659): 771-778, 2023 08 18.
Article
em En
| MEDLINE
| ID: mdl-37590346
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Telômero
/
Proteínas de Ligação a Telômeros
/
Complexo Shelterina
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos