title: 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.
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.
authors.affiliation: Department of Biology Education, Seoul National University, Seoul, Korea.
authors.forename: Soon-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Im
authors.forename: Sung-Rye
authors.initials: SR
authors.lastname: Park
authors.forename: Sang-Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Hoe-Jeong
authors.initials: HJ
authors.lastname: Wang
authors.forename: Joon-Kyu
authors.initials: JK
authors.lastname: Lee
mesh_terms: D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008898:Mimosine / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C544202:WDHD1 protein, human; D008898:Mimosine