Mechanism of PCNA loading by Ctf18-RFC for leading-strand DNA synthesis.
Science
; 385(6708): eadk5901, 2024 Aug 02.
Article
en En
| MEDLINE
| ID: mdl-39088616
ABSTRACT
The proliferating cell nuclear antigen (PCNA) clamp encircles DNA to hold DNA polymerases (Pols) to DNA for processivity. The Ctf18-RFC PCNA loader, a replication factor C (RFC) variant, is specific to the leading-strand Pol (Polε). We reveal here the underlying mechanism of Ctf18-RFC specificity to Polε using cryo-electron microscopy and biochemical studies. We found that both Ctf18-RFC and Polε contain specific structural features that direct PCNA loading onto DNA. Unlike other clamp loaders, Ctf18-RFC has a disordered ATPase associated with a diverse cellular activities (AAA+) motor that requires Polε to bind and stabilize it for efficient PCNA loading. In addition, Ctf18-RFC can pry prebound Polε off of DNA, then load PCNA onto DNA and transfer the PCNA-DNA back to Polε. These elements in both Ctf18-RFC and Polε provide specificity in loading PCNA onto DNA for Polε.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antígeno Nuclear de Célula en Proliferación
/
Replicación del ADN
/
Proteína de Replicación C
Límite:
Humans
Idioma:
En
Revista:
Science
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos