Structures of the human CST-Polα-primase complex bound to telomere templates.
Nature
; 608(7924): 826-832, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35830881
ABSTRACT
The mammalian DNA polymerase-α-primase (Polα-primase) complex is essential for DNA metabolism, providing the de novo RNA-DNA primer for several DNA replication pathways1-4 such as lagging-strand synthesis and telomere C-strand fill-in. The physical mechanism underlying how Polα-primase, alone or in partnership with accessory proteins, performs its complicated multistep primer synthesis function is unknown. Here we show that CST, a single-stranded DNA-binding accessory protein complex for Polα-primase, physically organizes the enzyme for efficient primer synthesis. Cryogenic electron microscopy structures of the CST-Polα-primase preinitiation complex (PIC) bound to various types of telomere overhang reveal that template-bound CST partitions the DNA and RNA catalytic centres of Polα-primase into two separate domains and effectively arranges them in RNA-DNA synthesis order. The architecture of the PIC provides a single solution for the multiple structural requirements for the synthesis of RNA-DNA primers by Polα-primase. Several insights into the template-binding specificity of CST, template requirement for assembly of the CST-Polα-primase PIC and activation are also revealed in this study.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Moldes Genéticos
/
Telômero
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DNA Primase
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Complexo Shelterina
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article