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The functional role of Cdc6 in S–G2/M in mammalian cells
Author(s) -
Lau Eric,
Zhu Changjun,
Abraham Robert T,
Jiang Wei
Publication year - 2006
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400624
Subject(s) - origin recognition complex , control of chromosome duplication , eukaryotic dna replication , pre replication complex , s phase , dna replication , dna replication factor cdt1 , microbiology and biotechnology , biology , licensing factor , minichromosome maintenance , chromatin , mitosis , replication factor c , dna re replication , genetics , dna
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.