ArticleMolecular and cellular biology2007
The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 1 of them a synthesis that pooled it.
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Who cites it
153 citing papers in PubMed, 1 synthesis or guideline pooled it, 235 citations in OpenAlex.
- Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor.Nature genetics · 2017Pooled it
- Proteasomal-dependent CHK1 degradation leads to DNA damage accumulation in ALS cellular model systems.Cell death & disease · 2026Article
- TIPIN coordinates ATM-dependent checkpoint and NF-κB signaling to counteract DNA replication damage from topoisomerase inhibition.Communications 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
- Single-molecule characterization of SV40 replisome and novel factors: human FPC and Mcm10.Nucleic acids research · 2024Article
- The TIMELESS and PARP1 interaction suppresses replication-associated DNA gap accumulation.Nucleic acids research · 2024Article
- The MCM2-7 Complex: Roles beyond DNA Unwinding.Biology · 2024Review
- Poly(ADP-ribosyl)ation of TIMELESS limits DNA replication stress and promotes stalled fork protection.Cell reports · 2024Article
- Review
- 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
- 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
- Review
- Creation and resolution of non-B-DNA structural impediments during replication.Critical reviews in biochemistry and molecular biology · 2022Article
- ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization.Cell reports · 2022Article
- The Fork Protection Complex: A Regulatory Hub at the Head of the Replisome.Sub-cellular biochemistry · 2022Article
- TIMELESS-TIPIN and UBXN-3 promote replisome disassembly during DNA replication termination in Caenorhabditis elegans.The EMBO journal · 2021Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
UV-induced DNA damage stalls DNA replication forks and activates the intra-S checkpoint to inhibit replicon initiation. In response to stalled replication forks, ATR phosphorylates and activates the transducer kinase Chk1 through interactions with the mediator proteins TopBP1, Claspin, and Timeless (Tim). Murine Tim recently was shown to form a complex with Tim-interacting protein (Tipin), and a similar complex was shown to exist in human cells. Knockdown of Tipin using small interfering RNA reduced the expression of Tim and reversed the intra-S checkpoint response to UVC. Tipin interacted with replication protein A (RPA) and RPA-coated DNA, and RPA promoted the loading of Tipin onto RPA-free DNA. Immunofluorescence analysis of spread DNA fibers showed that treating HeLa cells with 2.5 J/m(2) UVC not only inhibited the initiation of new replicons but also reduced the rate of chain elongation at active replication forks. The depletion of Tim and Tipin reversed the UV-induced inhibition of replicon initiation but affected the rate of DNA synthesis at replication forks in different ways. In undamaged cells depleted of Tim, the apparent rate of replication fork progression was 52% of the control. In contrast, Tipin depletion had little or no effect on fork progression in unirradiated cells but significantly attenuated the UV-induced inhibition of DNA chain elongation. Together, these findings indicate that the Tim-Tipin complex mediates the UV-induced intra-S checkpoint, Tim is needed to maintain DNA replication fork movement in the absence of damage, Tipin interacts with RPA on DNA and, in UV-damaged cells, Tipin slows DNA chain elongation in active replicons.
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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.