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Updated: Aug 14, 2026
Detection of DNA Double-Stranded Breaks in Mouse Oocytes
Published on: June 23, 2023
DNA damage checkpoints in mammals
Hiroyuki Niida1, Makoto Nakanishi
1Department of Biochemistry and Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Abstract:
DNA damage is a common event and probably leads to mutation or deletion within chromosomal DNA, which may cause cancer or premature aging. DNA damage induces several cellular responses including DNA repair, checkpoint activity and the triggering of apoptotic pathways. DNA damage checkpoints are associated with biochemical pathways that end delay or arrest of cell-cycle progression. These checkpoints engage damage sensor proteins, such as the Rad9-Rad1-Hus1 (9-1-1) complex, and the Rad17-RFC complex, in the detection of DNA damage and transduction of signals to ATM, ATR, Chk1 and Chk2 kinases. Chk1 and Chk2 kinases regulate Cdc25, Wee1 and p53 that ultimately inactivate cyclin-dependent kinases (Cdks) which inhibit cell-cycle progression. In this review, we discuss the molecular mechanisms by which DNA damage is recognized by sensor proteins and signals are transmitted to Cdks. We classify the genes involved in checkpoint signaling into four categories, namely sensors, mediators, transducers and effectors, although their proteins have the broad activity, and thus this classification is for convenience and is not definitive.
Insights
DNA damage triggers cellular responses like repair and cell cycle arrest. This review details how sensor proteins detect damage and signal kinases to halt cell division, preventing mutations.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- DNA damage is a frequent occurrence with potential to cause cancer and aging.
- Cellular responses to DNA damage include repair, checkpoint activation, and apoptosis.
- DNA damage checkpoints involve complex signaling pathways that arrest cell-cycle progression.
Purpose of the Study:
- To review the molecular mechanisms of DNA damage recognition and signal transduction.
- To classify genes involved in DNA damage checkpoint signaling.
Main Methods:
- Review of literature on DNA damage response pathways.
- Analysis of sensor proteins (e.g., 9-1-1 complex, Rad17-RFC complex).
- Discussion of kinase signaling cascades (ATM, ATR, Chk1, Chk2) and their targets (Cdc25, Wee1, p53).
Main Results:
- DNA damage is detected by sensor proteins that initiate signaling cascades.
- Kinases like Chk1 and Chk2 regulate cell cycle inhibitors (Cdc25, Wee1, p53) to arrest cell division.
- Genes in checkpoint signaling can be categorized into sensors, mediators, transducers, and effectors.
Conclusions:
- Understanding DNA damage recognition and signaling is crucial for comprehending cancer and aging.
- The intricate network of sensor proteins and kinases ensures genomic integrity.
- Classification of checkpoint genes aids in dissecting the complex DNA damage response.
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