ArticleThe Journal of biological chemistry2016
TIMELESS Suppresses the Accumulation of Aberrant CDC45·MCM2-7·GINS Replicative Helicase Complexes on Human Chromatin.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- RECQ4 arginine methylation suppresses single-stranded DNA gap accumulation at replication forks.Nucleic acids research · 2026Article
- Two fork protection complexes at the replication fork play distinct roles in fork progression and stress response.Research square · 2026Article
- A new model for coordinating the functions of TIMELESS at the replication fork.bioRxiv : the preprint server for biology · 2025Article
- Article
- ZFP36 loss-mediated BARX1 stabilization promotes malignant phenotypes by transactivating master oncogenes in NSCLC.Cell death & disease · 2023Article
- The TIMELESS effort for timely DNA replication and protection.Cellular and molecular life sciences : CMLS · 2023Review
- DNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation.Nature communications · 2023Article
- Article
- CDC45 modulates MCM7 expression and inhibits cell proliferation by suppressing the PI3K/AKT pathway in acute myeloid leukemia.American journal of translational research · 2021Article
- Molecular Mechanisms of the RECQ4 Pathogenic Mutations.Frontiers in molecular biosciences · 2021Review
- Pathogenic mutations reveal a role of RECQ4 in mitochondrial RNA:DNA hybrid formation and resolution.Scientific reports · 2020Article
- G2G: A web-server for the prediction of human synthetic lethal interactions.Computational and structural biotechnology journal · 2020Article
- Regulation of the initiation of DNA replication in human cells.DNA repair · 2018Review
- SUMO2 conjugation of PCNA facilitates chromatin remodeling to resolve transcription-replication conflicts.Nature communications · 2018Article
- [Deguelin inhibits proliferation and regulates the expression of MCM3-CDC45 in MCF-7 and H1299 cells in vitro].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017Article
- Advances in the Study of Circadian Genes in Non-Small Cell Lung Cancer.Integrative cancer therapiesArticle
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The replication licensing factor CDC6 recruits the MCM2-7 replicative helicase to the replication origin, where MCM2-7 is activated to initiate DNA replication. MCM2-7 is activated by both the CDC7-Dbf4 kinase and cyclin-dependent kinase and via interactions with CDC45 and go-ichi-ni-san complex (GINS) to form the CDC45·MCM2-7·GINS (CMG) helicase complex. TIMELESS (TIM) is important for the subsequent coupling of CMG activity to DNA polymerases for efficient DNA synthesis. However, the mechanism by which TIM regulates CMG activity for proper replication fork progression remains unclear. Here we show that TIM interacts with MCM2-7 prior to the initiation of DNA replication. TIM depletion in various human cell lines results in the accumulation of aberrant CMG helicase complexes on chromatin. Importantly, the presence of these abnormal CMG helicase complexes is not restricted to cells undergoing DNA synthesis. Furthermore, even though these aberrant CMG complexes interact with the DNA polymerases on human chromatin, these complexes are not phosphorylated properly by cyclin-dependent kinase/CDC7-Dbf4 kinase and exhibit reduced DNA unwinding activity. This phenomenon coincides with a significant accumulation of the p27 and p21 replication inhibitors, reduced chromatin association of CDC6 and cyclin E, and a delay in S phase entry. Our results provide the first evidence that TIM is required for the correct chromatin association of the CMG complex to allow efficient DNA replication.
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Registered trials
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.