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Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
Published on: June 8, 2018
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Cell cycle-dependent resolution of DNA double-strand breaks
Susanna Ambrosio1, Giacomo Di Palo2, Giuliana Napolitano1
1Department of Biology, University of Naples 'Federico II', Naples, Italy.
Oncotarget
|December 25, 2015
Summary
DNA double-strand breaks (DSBs) in quiescent cells are not repaired, leading to sustained p53 activation. Damaged quiescent cells show inefficient repair upon cell cycle re-entry, highlighting cell-cycle state dependence of DNA repair.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- DNA double-strand breaks (DSBs) trigger the DNA damage response (DDR).
- DDR induces cell-cycle arrest to prevent replication or mitosis with damaged DNA.
- Mammalian tissues have both proliferating and quiescent cells, suggesting potential differences in DDR.
Purpose of the Study:
- To investigate differences in DDR and DSB repair between proliferating and quiescent cells.
- To analyze the recruitment and resolution of DSB repair factors in different cell-cycle states.
Main Methods:
- Induction of site-specific DSBs in asynchronously proliferating, G0-arrested, and G1-arrested cells.
- Studying the recruitment of DSB repair factors.
- Monitoring the resolution of DNA lesions and p53 pathway activation.
Main Results:
- DSBs in G0 quiescent cells are unrepaired and sustain p53 pathway activation.
- Damaged G0 cells exhibit delayed clearance of DSB repair factors upon cell cycle re-entry, indicating inefficient repair.
- Initial DSB recognition and repair factor assembly are similar across proliferating, G0, and G1-arrested cells.
Conclusions:
- DSB repair efficiency and resolution are critically dependent on the cell-cycle state.
- Quiescent cells display a distinct and less efficient DSB repair mechanism compared to proliferating cells.
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