Mimosine arrests the cell cycle prior to the onset of DNA replication by preventing the binding of human Ctf4/And-1 to chromatin via Hif-1α activation in HeLa cells.
Cell Cycle
; 11(4): 761-6, 2012 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-22374673
ABSTRACT
Though the G(1) checkpoint in mammalian cells has been known for decades, the molecular targets that prevent S-phase entry remain unknown. Mimosine is a rare plant amino acid that arrests the cell cycle in the G(1) phase before entry into S phase. Here, we show that mimosine interrupts the binding of Ctf4 to chromatin, which is essential for the initiation of DNA replication in HeLa cells, and this effect is mediated by the Hif-1α-dependent increase in the level of p27. Depletion of Hif-1α results in an increased binding of Ctf4 to chromatin and the entry of cells into S phase even in the presence of mimosine. These results suggest that the binding of Ctf4 to chromatin is the target of the Hif-1α-dependent checkpoint pathway for cell cycle arrest in G(1) phase. Although we observed Hif-1α-dependent arrest in mimosine-treated cells, it is possible that Ctf4 may act as a common target for G(1) arrest in various other checkpoint pathways.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cromatina
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Ciclo Celular
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Proteínas de Unión al ADN
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Replicación del ADN
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Subunidad alfa del Factor 1 Inducible por Hipoxia
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Mimosina
Límite:
Humans
Idioma:
En
Año:
2012
Tipo del documento:
Article