The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells
Open accessAbstract
The Per1 gene is a core clock factor that plays an essential role in generating circadian rhythms. Recent data reveal that major biological pathways, including those critical to cell division, are under circadian control. We report here that Per1 provides an important link between the circadian system and the cell cycle system. Overexpression of Per1 sensitized human cancer cells to DNA damage-induced apoptosis; in contrast, inhibition of Per1 in similarly treated cells blunted apoptosis. The apoptotic phenotype was associated with altered expression of key cell cycle regulators. In addition, Per1 interacted with the checkpoint proteins ATM and Chk2. Ectopic expression of Per1 in human cancer cell lines led to significant growth reduction. Finally, Per1 levels were reduced in human cancer patient samples. Our results highlight the importance of circadian regulation to fundamental cellular functions and support the hypothesis that disruption of core clock genes may lead to cancer development.
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Evidence from cellular and in vivo models indicates that core circadian genes have an important role in carcinogenesis.
“Emerging evidence in several different cellular and in vivo models points to an important role of the core circadian genes in carcinogenesis (Filipski et al., 2005; Fu et al., 2002; Gery et al., 2006; Janich et al., 2011; Kettner et al., 2014; Lee et al., 2010; Puram et al., 2016; Sahar and Sassone-Corsi, 2009; Van Dycke et al., 2015; Wood et al., 2008).”
From Circadian Rhythm Disruption Promotes Lung Tumorigenesis (2016) · cites this paper as Gery et al., 2006
Earlier reports using germline mutations in circadian components have highlighted a role for circadian rhythm disruption in tumor predisposition.
“Earlier reports using germline mutations in circadian components have highlighted a role for circadian rhythm disruption in tumor predisposition (Filipski et al., 2005; Fu et al., 2002; Gery et al., 2006; Janich et al., 2011; Kettner et al., 2014; Lee et al., 2010; Sahar and Sassone-Corsi, 2009; Van Dycke et al., 2015; Wood et al., 2008).”
From Circadian Rhythm Disruption Promotes Lung Tumorigenesis (2016) · cites this paper as Gery et al., 2006
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- Authors
- Gery, S., Komatsu, N., Baldjyan, L., Yu, A., Koo, D., & Koeffler, H. P.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Gery, Sigal
- ORCID
- Koeffler, H. Phillip
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 22
- Issue
- 3
- Pages
- 375-382
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2163183531
- Cited by
- 630
- References
- 35
- Citations by year
- 2026: 20 · 2025: 34 · 2024: 24 · 2023: 38 · 2022: 20 · 2021: 48 · 2020: 48 · 2019: 36 · 2018: 14 · 2017: 33 · 2016: 34 · 2015: 28 · 2014: 39 · 2013: 24 · 2012: 26
- FWCI
- 13.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Keywords
- Per1, clock genes, DNA damage-induced apoptosis, cell cycle regulation, ATM, Chk2, DNA damage checkpoint, cancer cell growth
- MeSH terms
- Circadian Rhythm, DNA Damage, Humans, Neoplasms, Nuclear Proteins, Protein Binding, Protein-Tyrosine Kinases, Radiation, Ionizing, RNA, Messenger, Tumor Cells, Cultured, Down-Regulation, Up-Regulation, Gene Expression, Gene Expression Regulation, Neoplastic, CDC2 Protein Kinase, Cyclins, Apoptosis, Cell Cycle Proteins, HCT116 Cells, Cell Line, Tumor, Cell Growth Processes, Cyclin-Dependent Kinase Inhibitor p21, Period Circadian Proteins
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