ArticleCell cycle (Georgetown, Tex.)2016
Cdc45 is limiting for replication initiation in humans.
Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 81 citations in OpenAlex.
- CD8 T lymphocytes deploy embryonic cell cycle control mechanisms for rapid cell proliferation.EMBO reports · 2026Article
- Replication origin firing capacity indicates ATR inhibitor sensitivity.Nature communications · 2026Article
- Topological stress regulates replication fork dynamics in unperturbed S phase.Nature communications · 2026Article
- Genome-wide transcriptional profiling identifies molecular markers associated with early carcinogenesis in high-grade bladder cancer.Scientific reports · 2026Article
- Autosomal dominant CDC45 deficiency with allelic expression bias causes a novel genetic disease of the immune system.bioRxiv : the preprint server for biology · 2026Article
- Parallel Selection for Longevity in Mammals and Birds.bioRxiv : the preprint server for biology · 2025Article
- Mammalian H4K16ac regulates the spatiotemporal order of genome replication rather than gene expression.Nucleic acids research · 2025Article
- Heat shock transcription factor-mediated thermal tolerance and cell size plasticity in marine diatoms.Nature communications · 2025Article
- HROB Is Implicated in DNA Replication.Genes · 2024Article
- Induction of the humanMolecular medicine reports · 2024Article
- Deciphering the molecular functionality of Cdc45 in replisomal complex.Biochemistry and biophysics reports · 2024Article
- Quantity and quality of minichromosome maintenance protein complexes couple replication licensing to genome integrity.Communications biology · 2024Review
- The combination of brentuximab vedotin and chidamide synergistically suppresses the proliferation of T-cell lymphoma cells through the enhancement of apoptosis.Cancer chemotherapy and pharmacology · 2024Article
- LowTheranostics · 2024Article
- Unwinding the Role of the CMG Helicase in Inborn Errors of Immunity.Journal of clinical immunology · 2023Article
- H4S47 O-GlcNAcylation regulates the activation of mammalian replication origins.Nature structural & molecular biology · 2023Article
- Ring finger protein 126 promotes breast cancer metastasis and serves as a potential target to improve the therapeutic sensitivity of ATR inhibitors.Breast cancer research : BCR · 2022Article
- Systematic pan‑cancer analysis identifies CDC45 as having an oncogenic role in human cancers.Oncology reports · 2022Article
- Article
- High abundance of CDC45 inhibits cell proliferation through elevation of HSPA6.Cell proliferation · 2022Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cdc45 is an essential protein that together with Mcm2-7 and GINS forms the eukaryotic replicative helicase CMG. Cdc45 seems to be rate limiting for the initial unwinding or firing of replication origins. In line with this view, Cdc45-overexpressing cells fired at least twice as many origins as control cells. However, these cells displayed an about 2-fold diminished fork elongation rate, a pronounced asymmetry of replication fork extension, and an early S phase arrest. This was accompanied by H2AX-phosphorylation and subsequent apoptosis. Unexpectedly, we did not observe increased ATR/Chk1 signaling but rather a mild ATM/Chk2 response. In addition, we detected accumulation of long stretches of single-stranded DNA, a hallmark of replication catastrophe. We conclude that increased origin firing by upregulated Cdc45 caused exhaustion of the single-strand binding protein RPA, which in consequence diminished the ATR/Chk1 response; the subsequently occurring fork breaks led to an ATM/Chk2 mediated phosphorylation of H2AX and eventually to apoptosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.