Quantitative proteomics reveals a "poised quiescence" cellular state after triggering the DNA replication origin activation checkpoint.

ABSTRACT: An origin activation checkpoint has recently been discovered in the G1 phase of the mitotic cell cycle, which can be triggered by loss of DNA replication initiation factors such as the Cdc7 kinase. Insufficient levels of Cdc7 activate cell cycle arrest in normal cells, whereas cancer cells appear to lack this checkpoint response, do not arrest, and proceed with an abortive S phase, leading to cell death. The differential response between normal and tumor cells at this checkpoint has led to widespread interest in the development of pharmacological Cdc7 inhibitors as novel anticancer agents. We have used RNAi against Cdc7 in combination with SILAC-based high resolution MS proteomics to investigate the cellular mechanisms underlying the maintenance of the origin activation checkpoint in norma

SUBMITTER: Mulvey C 

PROVIDER: S-EPMC4261600 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature