Coupling of Human Circadian and Cell Cycles by the Timeless Protein
Open accessAbstract
The Timeless protein is essential for circadian rhythm in Drosophila. The Timeless orthologue in mice is essential for viability and appears to be required for the maintenance of a robust circadian rhythm as well. We have found that the human Timeless protein interacts with both the circadian clock protein cryptochrome 2 and with the cell cycle checkpoint proteins Chk1 and the ATR-ATRIP complex and plays an important role in the DNA damage checkpoint response. Down-regulation of Timeless in human cells seriously compromises replication and intra-S checkpoints, indicating an intimate connection between the circadian cycle and the DNA damage checkpoints that is in part mediated by the Timeless protein.
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The Tim-Tipin complex associates with ATR-Chk1 checkpoint proteins and plays an essential role in the DNA damage response.
“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 [130]
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References 43 · Cited by 310
Research works printed but not linked: 1
- Nghiem, P., P. K. Park, Y. Kim, C. Vaziri, and S. L. Schreiber. 2001. ATR inhibition selectively sensitizes G1 checkpoint-deficient cells to lethal pre- mature chromatin condensation. Proc. Natl. Acad. Sci. USA 98:9092-9097.
- Authors
- Ünsal-Kaçmaz, K., Mullen, T. E., Kaufmann, W. K., & Sancar, A.
- Affiliations
- Department of Biochemistry and Biophysics
- Cancer Cell Biology Training Program
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Sancar, Aziz
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2005-04-01
- Volume
- 25
- Issue
- 8
- Pages
- 3109-3116
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1069621
- OpenAlex
- W2164585152
- Cited by
- 310
- References
- 43
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 8 · 2023: 7 · 2022: 10 · 2021: 14 · 2020: 16 · 2019: 14 · 2018: 12 · 2017: 14 · 2016: 19 · 2015: 21 · 2014: 24 · 2013: 12 · 2012: 19
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- University of Southern California
- Florida State University
- National Institutes of Health (GM31082, CA-16086, ES10126)
- National Cancer Institute (P30CA 16086, CA-160-86, CA 81343, R01CA081343, P30CA016086)
- National Institute of General Medical Sciences (R01GM032833, R01GM031082, GM310.82, R37GM031082, GM32833)
- National Institute of Environmental Health Sciences (P30ES10126), P30ES010126)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- circadian clock, cell cycle, CRY2, Chk1, DNA damage checkpoint, S-phase checkpoint, DNA replication, circadian rhythm, protein-protein interaction
- MeSH terms
- Checkpoint Kinase 1, Cell Cycle, Cell Line, Circadian Rhythm, DNA Damage, DNA Replication, DNA-Binding Proteins, Exodeoxyribonucleases, Flavoproteins, Humans, Hydroxyurea, Phosphoproteins, Protein Kinases, Transcription Factors, Down-Regulation, Protein Serine-Threonine Kinases, Cell Cycle Proteins, RNA, Small Interfering, Chromatin Assembly and Disassembly, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Cryptochromes, Ataxia Telangiectasia Mutated Proteins
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