title: The functional role of Cdc6 in S-G2/M in mammalian cells.
abstract: The Cdc6 protein is required for licensing of replication origins before the onset of DNA replication in eukaryotic cells. Here, we examined whether Cdc6 has other roles in mammalian cell-cycle progression from S to G2/M phase. Using RNA interference, we showed that depletion of Cdc6 in synchronous G1 cells blocks G1 to S transition, confirming the essential role of Cdc6 in the initiation of DNA replication. In contrast, depletion of Cdc6 in synchronous S-phase cells slowed DNA replication and led to mitotic lethality. The Cdc6-depleted S-phase cells showed fewer newly fired origins; however, established replication forks remained active, even during chromatin condensation. Despite such DNA replication abnormalities, loss of Cdc6 failed to activate Chk1 kinase. These results show that Cdc6 is not only required for G1 origin licensing, but is also crucial for proper S-phase DNA replication that is essential for DNA segregation during mitosis.
authors.affiliation: The Burnham Institute, La Jolla, California 92037, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Lau
authors.forename: Changjun
authors.initials: C
authors.lastname: Zhu
authors.forename: Robert T
authors.initials: RT
authors.lastname: Abraham
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D000071877:Checkpoint Kinase 1; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D016195:G2 Phase; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016196:S Phase
chemical_list: C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D004247:DNA; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1