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Data show that MRE11- and RAD51-dependent fork repair leading to reloading of the GINS onto the MCM-CDC45 complex still engaged with the DNA could be sufficient to restore a functional CDC45-MCM-GINS (CMG) helicase complex.
The size and relative position of the three helices (alpha2, alpha7 and alpha8) that contribute to the active site architecture are highly conserved between Cdc45 and RecJ, whereas the helical structure on the solvent-exposed DHH (显示 DHH 蛋白) side (alpha3, alpha4 and alpha5) shows more conformational variability.
strong evidence that Cdc45 directly loads RPA on the emerging nascent ssDNA
Date show that when Wee1 (显示 WEE1 蛋白) alone is inhibited, Chk1 (显示 CHEK1 蛋白) suppresses CDC45 loading and thereby limits the extent of unscheduled replication initiation and subsequent S-phase DNA damage, despite very high CDK (显示 CDK4 蛋白)-activity.
The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.
Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis
ectopic expression of Cdc45 led to increased firing of replication origins, severe replication stress, an early S-phase arrest, replication fork stalling, and eventually cell death by apoptosis.
The depletion of HDHB (显示 HELB 蛋白) from human cells diminishes Cdc45 association with chromatin, suggesting that HDHB (显示 HELB 蛋白) may facilitate Cdc45 recruitment at G1/S in human cells.
Data suggest that CDC45 and MCM10 (minichromosome maintenance complex component 10 (显示 MCM10 蛋白)) directly interact and establish a mutual co-operation in DNA binding; key domains appear to interact and then interact with DNA inside cells or in cell-free systems.
CDC45 directly interact with MCM2-7 (显示 MCM2 蛋白) proteins; with PSF2 (显示 TAP2 蛋白), PSF3 (显示 GINS3 蛋白) and SLD5 (显示 GINS4 蛋白) in GINS subunits; and with replication protein A2 (显示 RPA2 蛋白), AND-1. A considerable portion of CDC45 localizes in a region other than the DNA replication forks in nuclei.
After UV-damage, Cdc45 is still present in a large multi-protein complex and that its mobility within living cells is consistently similar following UVC-mediated DNA damage.
Cdc45 Recapitulates Myc (显示 MYC 蛋白)-Dependent DNA Replication Stress.
MCM4 (显示 MCM4 蛋白) phosphorylation by Cdc7 (显示 CDC7 蛋白) kinase facilitates its interaction with Cdc45 on chromatin
The protein encoded by this gene was identified by its strong similarity with Saccharomyces cerevisiae Cdc45, an essential protein required to the initiation of DNA replication. Cdc45 is a member of the highly conserved multiprotein complex including Cdc6/Cdc18, the minichromosome maintenance proteins (MCMs) and DNA polymerase, which is important for early steps of DNA replication in eukaryotes. This protein has been shown to interact with MCM7 and DNA polymerase alpha. Studies of the similar gene in Xenopus suggested that this protein play a pivotal role in the loading of DNA polymerase alpha onto chromatin. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.
CDC45 cell division cycle 45 homolog
, cell division cycle 45 homolog
, CDC45 cell division cycle 45-like
, CDC45-related protein
, cell division control protein 45 homolog
, cell division cycle 45-like 2
, human CDC45