Cryo-EM structure of the human CST-Polα/primase complex in a recruitment state.
Nat Struct Mol Biol
; 29(8): 813-819, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35578024
ABSTRACT
The CST-Polα/primase complex is essential for telomere maintenance and functions to counteract resection at double-strand breaks. We report a 4.6-Å resolution cryo-EM structure of human CST-Polα/primase, captured prior to catalysis in a recruitment state stabilized by chemical cross-linking. Our structure reveals an evolutionarily conserved interaction between the C-terminal domain of the catalytic POLA1 subunit and an N-terminal expansion in metazoan CTC1. Cross-linking mass spectrometry and negative-stain EM analysis provide insight into CST binding by the flexible POLA1 N-terminus. Finally, Coats plus syndrome disease mutations previously characterized to disrupt formation of the CST-Polα/primase complex map to protein-protein interfaces observed in the recruitment state. Together, our results shed light on the architecture and stoichiometry of the metazoan fill-in machinery.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Primase
/
Proteínas de Ligação a Telômeros
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Struct Mol Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos