Related Experiment Video
Updated: May 27, 2026
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
Regulatory networks integrating cell cycle control with DNA damage checkpoints and double-strand break repair
1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Abstract:
Double-strand breaks (DSBs), arising from exposure to exogenous clastogens or as a by-product of endogenous cellular metabolism, pose grave threats to genome integrity. DSBs can sever whole chromosomes, leading to chromosomal instability, a hallmark of cancer. Healing broken DNA takes time, and it is therefore essential to temporarily halt cell division while DSB repair is underway. The seminal discovery of cyclin-dependent kinases as master regulators of the cell cycle unleashed a series of studies aimed at defining how the DNA damage response network delays cell division. These efforts culminated with the identification of Cdc25, the protein phosphatase that activates Cdc2/Cdk1, as a critical target of the checkpoint kinase Chk1. However, regulation works both ways, as recent studies have revealed that Cdc2 activity and cell cycle position determine whether DSBs are repaired by non-homologous end-joining or homologous recombination (HR). Central to this regulation are the proteins that initiate the processing of DNA ends for HR repair, Mre11-Rad50-Nbs1 protein complex and Ctp1/Sae2/CtIP, and the checkpoint kinases Tel1/ATM and Rad3/ATR. Here, we review recent findings and provide insight on how proteins that regulate cell cycle progression affect DSB repair, and, conversely how proteins that repair DSBs affect cell cycle progression.
Insights
DNA double-strand breaks (DSBs) threaten genome integrity. Cell cycle regulation and DSB repair pathways are intricately linked, influencing each other to maintain genomic stability and prevent cancer.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- DNA double-strand breaks (DSBs) are critical DNA lesions that can lead to chromosomal instability and cancer.
- Cell cycle progression must be halted during DSB repair to maintain genome integrity.
- Cyclin-dependent kinases (CDKs) regulate the cell cycle, and their activity is influenced by DNA damage response (DDR) pathways.
Purpose of the Study:
- To review recent findings on the interplay between cell cycle regulation and DSB repair.
- To elucidate how cell cycle regulators impact DSB repair pathway choice.
- To understand how DSB repair proteins influence cell cycle progression.
Main Methods:
- Literature review of recent studies in molecular biology and genetics.
- Analysis of the roles of key proteins in cell cycle control and DNA repair.
- Integration of findings on checkpoint kinases, phosphatases, and DSB repair complexes.
Main Results:
- Cell cycle regulators, including Cdc25 and Cdc2/Cdk1, are critical targets of DDR pathways like Chk1.
- Cdc2 activity and cell cycle phase dictate the choice between non-homologous end-joining (NHEJ) and homologous recombination (HR) for DSB repair.
- Proteins involved in HR initiation (Mre11-Rad50-Nbs1, Ctp1/Sae2/CtIP) and checkpoint kinases (Tel1/ATM, Rad3/ATR) are central to this regulatory network.
Conclusions:
- There is a bidirectional regulatory relationship between cell cycle progression and DSB repair.
- Understanding this crosstalk is crucial for comprehending genome stability maintenance and cancer development.
- Future research should further explore the molecular mechanisms governing this intricate network.
Related Concept Videos
02:36DNA Damage Can Stall the Cell Cycle
02:36DNA Damage can Stall the Cell Cycle
01:28The Cell Cycle Control System
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
02:11The Cell Cycle Control System
02:11The Cell Cycle Control System
01:23Negative Regulator Molecules