Single-molecule imaging reveals the mechanism of bidirectional replication initiation in metazoa.
Cell
; 187(15): 3992-4009.e25, 2024 Jul 25.
Article
en En
| MEDLINE
| ID: mdl-38866019
ABSTRACT
Metazoan genomes are copied bidirectionally from thousands of replication origins. Replication initiation entails the assembly and activation of two CMG helicases (Cdc45â
Mcm2-7â
GINS) at each origin. This requires several replication firing factors (including TopBP1, RecQL4, and DONSON) whose exact roles are still under debate. How two helicases are correctly assembled and activated at each origin is a long-standing question. By visualizing the recruitment of GINS, Cdc45, TopBP1, RecQL4, and DONSON in real time, we uncovered that replication initiation is surprisingly dynamic. First, TopBP1 transiently binds to the origin and dissociates before the start of DNA synthesis. Second, two Cdc45 are recruited together, even though Cdc45 alone cannot dimerize. Next, two copies of DONSON and two GINS simultaneously arrive at the origin, completing the assembly of two CMG helicases. Finally, RecQL4 is recruited to the CMGâ
DONSONâ
DONSONâ
CMG complex and promotes DONSON dissociation and CMG activation via its ATPase activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Ciclo Celular
/
Replicación del ADN
/
Imagen Individual de Molécula
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos