Cell-cycle checkpoints and cancer
Abstract
All life on earth must cope with constant exposure to DNA-damaging agents such as the Sun's radiation. Highly conserved DNA-repair and cell-cycle checkpoint pathways allow cells to deal with both endogenous and exogenous sources of DNA damage. How much an individual is exposed to these agents and how their cells respond to DNA damage are critical determinants of whether that individual will develop cancer. These cellular responses are also important for determining toxicities and responses to current cancer therapies, most of which target the DNA.
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CHK1 prevents new origin firing by inhibiting CDK2 through CDC25A degradation, thus hindering the subsequent loading of CDC45 on chromatin to form the pre-initiation complex.
“CHK1 prevents new origin firing by inhibiting CDK2 through CDC25A degradation, thus hindering the subsequent loading of CDC45 on chromatin to form the pre-initiation complex [34].”
From The Spi1/PU.1 transcription factor accelerates replication fork progression by increasing PP1 phosphatase in leukemia (2017) · cites this paper as [34]
Mutations in checkpoint genes cause syndromes with increased cancer proneness or other clinical symptoms, especially neurological defects.
“The importance of the DNA damage checkpoint in the maintenance of genomic stability is underlined by the existence of many syndromes linked to mutations in checkpoint genes, causing increased cancer proneness or other clinical symptoms, especially neurological defects [13,14]”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [13]
p53-mutant mice are cancer prone but their predilection for mesenchymal and lymphoid malignancies rather than epithelial cancers does not match the tumor types most commonly possessing p53 mutations in humans.
“while p53-mutant mice are cancer prone, we noted that their predilection for mesenchymal and lymphoid malignancies, rather than epithelial cancers, did not represent the tumor types most commonly possessing p53 mutations in humans (101,102).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [101]
Components of DNA repair and DDR pathways have become therapeutic targets and are being tested in laboratory and clinical studies.
“factors involved in DNA repair and DDR pathways have become therapeutic targets and are currently being tested in both laboratory and clinical studies [151, 222]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [222]
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Maclean, K. H., Dorsey, F. C., Cleveland, J. L., & Kastan, M. B. (2007) · Journal of Clinical Investigation · doi:10.1172/jci33700 · Cited by 273 · see citing works
Self-citationBekker‐Jensen, S., Lukas, C., Melander, F., Bártek, J., & Lukas, J. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200503043 · Cited by 272 · see citing works
The pathways to tumor suppression via route p38
Han, J., & Sun, P. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.06.007 · Cited by 268 · see citing works
Rainey, M. D., Charlton, M. E., Stanton, R. V., & Kastan, M. B. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0763 · Cited by 267 · see citing works
Self-citation
- Authors
- Kastan, M. B., & Bartek, J.
- Affiliations
- St. Jude Children's Research Hospital (US)
- ORCID
- Kastan, Michael B.
- Venue
- Nature
- Published
- 2004-11
- Volume
- 432
- Issue
- 7015
- Pages
- 316-323
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1965239527
- Cited by
- 2,836
- References
- 98
- Citations by year
- 2026: 61 · 2025: 71 · 2024: 70 · 2023: 111 · 2022: 132 · 2021: 151 · 2020: 144 · 2019: 119 · 2018: 114 · 2017: 130 · 2016: 141 · 2015: 138 · 2014: 151 · 2013: 141 · 2012: 164
- FWCI
- 9.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- 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 › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- cell cycle checkpoints, DNA damage response, DNA repair, cancer, DNA-damaging agents, radiation, cancer therapy toxicity, carcinogenesis
- MeSH terms
- Animals, Cell Cycle, DNA Damage, Humans, Neoplasms, Signal Transduction
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