ArticleThe Journal of biological chemistry2014
Tipin functions in the protection against topoisomerase I inhibitor.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 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
- TOP1 and TOP2 complementarily maintain DNA replication fork progression in vertebrates.The Journal of biological chemistry · 2026Article
- Mechanisms controlling replication fork stalling and collapse at topoisomerase 1 cleavage complexes.Molecular cell · 2024Article
- REV3 promotes cellular tolerance to 5-fluorodeoxyuridine by activating translesion DNA synthesis and intra-S checkpoint.PLoS genetics · 2024Article
- TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation.Nature communications · 2023Article
- Vertebrate CTF18 and DDX11 essential function in cohesion is bypassed by preventing WAPL-mediated cohesin release.Genes & development · 2021Article
- Approaching Protein Barriers: Emerging Mechanisms of Replication Pausing in Eukaryotes.Frontiers in cell and developmental biology · 2021Review
- Separable functions of Tof1/Timeless in intra-S-checkpoint signalling, replisome stability and DNA topological stress.Nucleic acids research · 2020Article
- Fork pausing complex engages topoisomerases at the replisome.Genes & development · 2020Article
- Warsaw breakage syndrome DDX11 helicase acts jointly with RAD17 in the repair of bulky lesions and replication through abasic sites.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- AND-1 fork protection function prevents fork resection and is essential for proliferation.Nature communications · 2018Article
- Roles of eukaryotic topoisomerases in transcription, replication and genomic stability.Nature reviews. Molecular cell biology · 2016Review
- Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The replication fork temporarily stalls when encountering an obstacle on the DNA, and replication resumes after the barrier is removed. Simultaneously, activation of the replication checkpoint delays the progression of S phase and inhibits late origin firing. Camptothecin (CPT), a topoisomerase I (Top1) inhibitor, acts as a DNA replication barrier by inducing the covalent retention of Top1 on DNA. The Timeless-Tipin complex, a component of the replication fork machinery, plays a role in replication checkpoint activation and stabilization of the replication fork. However, the role of the Timeless-Tipin complex in overcoming the CPT-induced replication block remains elusive. Here, we generated viable TIPIN gene knock-out (KO) DT40 cells showing delayed S phase progression and increased cell death. TIPIN KO cells were hypersensitive to CPT. However, homologous recombination and replication checkpoint were activated normally, whereas DNA synthesis activity was markedly decreased in CPT-treated TIPIN KO cells. Proteasome-dependent degradation of chromatin-bound Top1 was induced in TIPIN KO cells upon CPT treatment, and pretreatment with aphidicolin, a DNA polymerase inhibitor, suppressed both CPT sensitivity and Top1 degradation. Taken together, our data indicate that replication forks formed without Tipin may collide at a high rate with Top1 retained on DNA by CPT treatment, leading to CPT hypersensitivity and Top1 degradation in TIPIN KO cells.
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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.