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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.
strong evidence that Cdc45 directly loads RPA on the emerging nascent ssDNA
Date show that when Wee1 (show WEE1 Proteins) alone is inhibited, Chk1 (show CHEK1 Proteins) suppresses CDC45 loading and thereby limits the extent of unscheduled replication initiation and subsequent S-phase DNA damage, despite very high CDK (show CDK4 Proteins)-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 (show HELB Proteins) from human cells diminishes Cdc45 association with chromatin, suggesting that HDHB (show HELB Proteins) may facilitate Cdc45 recruitment at G1/S in human cells.
Data suggest that CDC45 and MCM10 (minichromosome maintenance complex component 10 (show MCM10 Proteins)) 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 (show MCM2 Proteins) proteins; with PSF2 (show TAP2 Proteins), PSF3 (show GINS3 Proteins) and SLD5 (show GINS4 Proteins) in GINS subunits; and with replication protein A2 (show RPA2 Proteins), 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.
Data show that using a 200-nt primed circular DNA substrate, the combined action of DNA polymerase epsilon and the Cdc45/Mcm2-7 (show MCM2 Proteins)/GINS (CMG (show CASK Proteins) complex) leads to the formation of products >10 kb in length.
Cdc45 Recapitulates Myc (show MYC Proteins)-Dependent DNA Replication Stress.
MCM4 (show MCM4 Proteins) phosphorylation by Cdc7 (show CDC7 Proteins) 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