ArticleProceedings of the National Academy of Sciences of the United States of America2013
Human Tim-Tipin complex affects the biochemical properties of the replicative DNA helicase and DNA polymerases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 71 citations in OpenAlex.
- Germline polymorphisms in genes maintaining the replication fork predict the efficacy of oxaliplatin and irinotecan in patients with metastatic colorectal cancer.British journal of cancer · 2022Trial
- TIMELESS promotes glioma stemness and malignancy through JAK-STAT3 pathway.The Journal of biological chemistry · 2026Article
- Rac1 GTPase Regulates the SCFCancers · 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
- Comparative DNA methylation reveals epigenetic adaptation to high altitude in snub-nosed monkeys.Zoological research · 2024Article
- Intrinsic PARG inhibitor sensitivity is mimicked byNAR cancer · 2024Article
- Assessment of pulmonary fibrosis using weighted gene co-expression network analysis.Frontiers in toxicology · 2024Article
- Timeless-Tipin interactions with MCM and RPA mediate DNA replication stress response.Frontiers in cell and developmental biology · 2024Article
- Single cell RNA sequencing reveals endothelial cell killing and resolution pathways in experimental malaria-associated acute respiratory distress syndrome.PLoS pathogens · 2024Article
- Replisome dysfunction upon inducible TIMELESS degradation synergizes with ATR inhibition to trigger replication catastrophe.Nucleic acids research · 2023Article
- The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork.International journal of molecular sciences · 2023Review
- The TIMELESS effort for timely DNA replication and protection.Cellular and molecular life sciences : CMLS · 2023Review
- The Interplay of Cohesin and the Replisome at Processive and Stressed DNA Replication Forks.Cells · 2021Review
- Article
- A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity.Cancers · 2021Review
- TIMELESS inhibits breast cancer cell invasion and metastasis by down-regulating the expression of MMP9.Cancer cell international · 2021Article
- Approaching Protein Barriers: Emerging Mechanisms of Replication Pausing in Eukaryotes.Frontiers in cell and developmental biology · 2021Review
- Construction of Gene Modules and Analysis of Prognostic Biomarkers for Cervical Cancer by Weighted Gene Co-Expression Network Analysis.Frontiers in oncology · 2021Article
- Separable functions of Tof1/Timeless in intra-S-checkpoint signalling, replisome stability and DNA topological stress.Nucleic acids research · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Tim (Timeless) and Tipin (Tim-interacting protein) form a stable heterodimeric complex that influences checkpoint responses and replication fork progression. We report that the Tim-Tipin complex interacts with essential replication fork proteins and affects their biochemical properties. The Tim-Tipin complex, reconstituted and purified using the baculovirus expression system, interacts directly with Mcm complexes and inhibits the single-stranded DNA-dependent ATPase activities of the Mcm2-7 and Mcm4/6/7 complexes, the DNA unwinding activity of the Mcm4/6/7 complex, and the DNA unwinding and ATPase activity of Cdc45-Mcm2-7-GINS complex, the presumed replicative DNA helicase in eukaryotes. Although stable interactions between Tim-Tipin and DNA polymerases (pols) were not observed in immunoprecipitation experiments with purified proteins, Tim was shown to interact with DNA pols α, δ, and ε in cells. Furthermore, the Tim-Tipin complex significantly stimulated the pol activities of DNA pols α, δ, and ε in vitro. The effects of Tim-Tipin on the catalytic activities of the Mcm complexes and DNA pols are mediated by the Tim protein alone, and distinct regions of the Tim protein are responsible for the inhibition of Mcm complex activities and stimulation of DNA pols. These results suggest that the Tim-Tipin complex might play a role in coupling DNA unwinding and DNA synthesis by directly affecting the catalytic activities of replication fork proteins.
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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.