ArticleNucleic acids research2021
The CRL4DTL E3 ligase induces degradation of the DNA replication initiation factor TICRR/TRESLIN specifically during S phase.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Adaptive Replication Fork Acceleration by CDK1-Cyclin B1 Sustains Genome Duplication despite Impaired Origin Firing.bioRxiv : the preprint server for biology · 2026Article
- Dynamic regulation of origin firing factors links CDK activity to dormant origin activation.Nature communications · 2026Article
- Article
- Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication.Nature communications · 2025Article
- Cell cycle-dependent TICRR/TRESLIN and MTBP chromatin binding mechanisms and patterns.Genome biology · 2025Article
- Dynamic regulation of origin firing factors links CDK activity to dormant origin activation.bioRxiv : the preprint server for biology · 2025Article
- The genetic dissection of fetal haemoglobin persistence in sickle cell disease in Nigeria.Human molecular genetics · 2024Article
- TopBP1 utilises a bipartite GINS binding mode to support genome replication.Nature communications · 2024Article
- Comprehensive Analysis of TICRR in Hepatocellular Carcinoma Based on Bioinformatics Analysis.Biochemical genetics · 2024Article
- TICRR Overexpression Enhances Disease Aggressiveness and Immune Infiltration of Cutaneous Melanoma.Pharmacogenomics and personalized medicine · 2024Article
- Neural network and kinetic modelling of human genome replication reveal replication origin locations and strengths.PLoS computational biology · 2023Article
- DNA replication timing: Biochemical mechanisms and biological significance.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- The TRESLIN-MTBP complex couples completion of DNA replication with S/G2 transition.Molecular cell · 2022Article
- The Role of MTBP as a Replication Origin Firing Factor.Biology · 2022Review
- DNA Replication Licensing Factors: Novel Targets for Cancer Therapy via Inhibiting the Stemness of Cancer Cells.International journal of biological sciences · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
A DNA replication program, which ensures that the genome is accurately and wholly replicated, is established during G1, before the onset of S phase. In G1, replication origins are licensed, and upon S phase entry, a subset of these will form active replisomes. Tight regulation of the number of active replisomes is crucial to prevent replication stress-induced DNA damage. TICRR/TRESLIN is essential for DNA replication initiation, and the level of TICRR and its phosphorylation determine the number of origins that initiate during S phase. However, the mechanisms regulating TICRR protein levels are unknown. Therefore, we set out to define the TICRR/TRESLIN protein dynamics throughout the cell cycle. Here, we show that TICRR levels are high during G1 and dramatically decrease as cells enter S phase and begin DNA replication. We show that degradation of TICRR occurs specifically during S phase and depends on ubiquitin ligases and proteasomal degradation. Using two targeted siRNA screens, we identify CRL4DTL as a cullin complex necessary for TICRR degradation. We propose that this mechanism moderates the level of TICRR protein available for replication initiation, ensuring the proper number of active origins as cells progress through S phase.
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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.