The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
The Human Tim/Tipin Complex Coordinates an Intra-S Checkpoint Response to UV That Slows Replication Fork Displacement
Open accessAbstract
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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“The circadian protein Tim (Timeless) -Tipin (Timeless-interacting protein) complex associates with ATR-Chk1 checkpoint proteins and plays an essential role in DDR as well [130–133].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [131]
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1 retracted
Wang, X., Guan, J., Hu, B., Weiss, R. S., Iliakis, G. E., & Wang, Y. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh243 · Cited by 26
RetractedMolecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints
Sancar, A., Lindsey-Boltz, L. A., Ünsal-Kaçmaz, K., & Linn, S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073723 · Cited by 3,317
Self-citationThe XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η
Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., & Hanaoka, F. (1999) · Nature · doi:10.1038/21447 · Cited by 1,292
The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis
Falck, J., Mailand, N., Syljuåsen, R. G., Bartek, J., & Lukas, J. (2001) · Nature · doi:10.1038/35071124 · Cited by 1,085
Jackson, D., & Pombo, A. (1998) · Journal of Cell Biology · doi:10.1083/jcb.140.6.1285 · Cited by 881
Radiosensitivity in ataxia-telangiectasia: a new explanation.
Painter, R. B., & Young, B. R. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.12.7315 · Cited by 795
TopBP1 Activates the ATR-ATRIP Complex
Kumagai, A., Lee, J., Yoo, H. Y., & Dunphy, W. G. (2006) · Cell · doi:10.1016/j.cell.2005.12.041 · Cited by 787
Byun, T. S., Pacek, M., Yee, M.-C., Walter, J. C., & Cimprich, K. A. (2005) · Genes & Development · doi:10.1101/gad.1301205 · Cited by 767
The DNA replication checkpoint response stabilizes stalled replication forks
Lopes, M., Cotta‐Ramusino, C., Pellicioli, A., Liberi, G., Plevani, P., Muzi-Falconi, M., Newlon, C. S., & Foiani, M. (2001) · Nature · doi:10.1038/35087613 · Cited by 749
hRAD30 Mutations in the Variant Form of Xeroderma Pigmentosum
Johnson, R. E., Kondratick, C. M., Prakash, S., & Prakash, L. (1999) · Science · doi:10.1126/science.285.5425.263 · Cited by 732
Flagged first, then by citations
Research works printed but not linked: 3
- Grisham J., 1983, Surv. Synth. Pathol. Res., 1, 49
- Heffernan T. P., J. Biol. Chem.
- 10.1001/archderm.1994.01690080084012 · DOI · Paper page
Cited by
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Chakraborty, A., Aziz, F., Roh, E., Le, L. T. M., Dey, R., Zhang, T., Rathore, M. G., Biswas, A. S., Bode, A. M., & Dong, Z. (2020) · Oncotarget · doi:10.18632/oncotarget.27572 · Cited by 3
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Zafar, F., & Nakagaw, T. (2011) · InTech eBooks · doi:10.5772/19284 · Cited by 2
Binding of MCM-interacting proteins to ATP-binding site in MCM6
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Zhao, Z.-Y., & Lee, C. C. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1262-6_6 · Cited by 6
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Klapacz, J., & Gollapudi, B. B. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.95611-3 · Cited by 2
Keszthelyi, A., Whale, A. J., Houseley, J. M., & Baxter, J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.04.551986 · Cited by 2
Khan, A., Lim, J. F., Lo, N., Patel, J. A., Haley, J. D., & Kim, H. (2025) · Communications Biology · doi:10.1038/s42003-025-09084-7 · Cited by 1
Cell Cycle Regulation and DNA Damage
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Zhu, J. H. W. (2015) · Transcriptomics Open Access · doi:10.4172/2329-8936.1000e108 · Cited by 1
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Dutta, A. (2008) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1108413.564460
Weinheimer, A. S., Paung, Y., Rageul, J., Khan, A., Ho, B., Tong, M., Alphonse, S., Seeliger, M. A., & Kim, H. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.09.490802
Pavani, R. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2019.tde-14032023-173149
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Hussain, S., Bisht, D., & Muthuswami, R. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.27.678965
Bianco, J. N. (2010) · theses.fr (ABES) · doi:10.70675/c5c5f7fbz5b45z423ezbc8azeb8ce3450ec3
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Zhang, S. (2016) · theses.fr (ABES) · doi:10.70675/378524f1ze627z4e3dzbcf5z15f09d7cce33
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Metadata
- Authors
- Ünsal-Kaçmaz, K., Chastain, P. D., Qu, P.-P., Minoo, P., Cordeiro-Stone, M., Sancar, A., & Kaufmann, W. K.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of Southern California (US)
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
- Corresponding author
- Kaufmann, William K.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2007-04-01
- Volume
- 27
- Issue
- 8
- Pages
- 3131-3142
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1899931
- OpenAlex
- W2127622729
- Cited by
- 240
- References
- 67
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 9 · 2023: 9 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 10 · 2018: 3 · 2017: 10 · 2016: 15 · 2015: 13 · 2014: 23 · 2013: 19 · 2012: 13
- FWCI
- 10.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Cancer Institute (R01CA055065, CA 55065, CA 81343, R01CA081343, P30CA016086)
- National Institute of General Medical Sciences (R01GM032833, GM32833)
- National Institute of Environmental Health Sciences (R01ES011012, ES11012, P30ES010126)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- S-phase checkpoint, UV-induced DNA damage, replication fork stalling, replication fork progression, DNA chain elongation, ATR-Chk1 signaling, TopBP1, Claspin, TIMELESS, replication protein A, UV-C radiation, DNA damage response
- MeSH terms
- Checkpoint Kinase 1, Amino Acid Sequence, Carrier Proteins, DNA, DNA Replication, DNA-Binding Proteins, Enzyme Activation, HeLa Cells, Humans, Idoxuridine, Models, Genetic, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Protein Kinases, Ultraviolet Rays, Down-Regulation, S Phase, Cell Cycle Proteins, Intracellular Signaling Peptides and Proteins, Replication Protein A, Xeroderma Pigmentosum Group A Protein
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