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Updated: Dec 26, 2025

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
Published on: June 8, 2018
Checkpoint Responses to DNA Double-Strand Breaks
David P Waterman1, James E Haber1, Marcus B Smolka2
1Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA;
Abstract:
Cells confront DNA damage in every cell cycle. Among the most deleterious types of DNA damage are DNA double-strand breaks (DSBs), which can cause cell lethality if unrepaired or cancers if improperly repaired. In response to DNA DSBs, cells activate a complex DNA damage checkpoint (DDC) response that arrests the cell cycle, reprograms gene expression, and mobilizes DNA repair factors to prevent the inheritance of unrepaired and broken chromosomes. Here we examine the DDC, induced by DNA DSBs, in the budding yeast model system and in mammals.
Insights
Cells activate a DNA damage checkpoint (DDC) to repair DNA double-strand breaks (DSBs). This response prevents cell death and cancer by halting the cell cycle and initiating DNA repair, studied in yeast and mammals.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Cells encounter DNA damage, including DNA double-strand breaks (DSBs), during each cell cycle.
- Unrepaired or improperly repaired DSBs can lead to cell lethality or cancer.
- The DNA damage checkpoint (DDC) response is a critical cellular mechanism to manage DSBs.
Purpose of the Study:
- To examine the DNA damage checkpoint (DDC) response induced by DNA double-strand breaks (DSBs).
- To investigate the conserved mechanisms of DDC in both budding yeast and mammalian systems.
Main Methods:
- Comparative analysis of DDC pathways.
- Utilizing budding yeast as a model organism.
- Investigating DDC in mammalian cells.
Main Results:
- The DDC response involves cell cycle arrest, gene expression reprogramming, and recruitment of DNA repair factors.
- Conserved elements of the DDC response exist between yeast and mammals.
- The DDC is essential for preventing the inheritance of damaged chromosomes.
Conclusions:
- The DNA damage checkpoint is a fundamental cellular process for maintaining genomic integrity.
- Understanding DDC mechanisms in model systems like yeast can provide insights into human disease, including cancer.
- The study highlights the conserved nature of DNA damage response pathways across eukaryotes.
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