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Updated: Dec 25, 2025
Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
Published on: June 8, 2018
How do cells sense DNA lesions?
Chiara Vittoria Colombo1, Marco Gnugnoli1, Elisa Gobbini1
1Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
Abstract:
DNA is exposed to both endogenous and exogenous DNA damaging agents that chemically modify it. To counteract the deleterious effects exerted by DNA lesions, eukaryotic cells have evolved a network of cellular pathways, termed DNA damage response (DDR). The DDR comprises both mechanisms devoted to repair DNA lesions and signal transduction pathways that sense DNA damage and transduce this information to specific cellular targets. These targets, in turn, impact a wide range of cellular processes including DNA replication, DNA repair and cell cycle transitions. The importance of the DDR is highlighted by the fact that DDR inactivation is commonly found in cancer and causes many different human diseases. The protein kinases ATM and ATR, as well as their budding yeast orthologs Tel1 and Mec1, act as master regulators of the DDR. The initiating events in the DDR entail both DNA lesion recognition and assembly of protein complexes at the damaged DNA sites. Here, we review what is known about the early steps of the DDR.
Insights
Eukaryotic cells possess a DNA damage response (DDR) network to repair DNA lesions. This review focuses on the early steps of DDR, involving DNA lesion recognition and protein complex assembly, crucial for preventing diseases like cancer.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- DNA is constantly damaged by internal and external factors.
- The DNA damage response (DDR) is a crucial cellular network that counteracts DNA lesions.
- Dysfunctional DDR is linked to cancer and other human diseases.
Purpose of the Study:
- To review the early events in the DNA damage response (DDR).
- To highlight the roles of key regulators like ATM and ATR kinases.
- To explain the initial recognition of DNA damage and complex assembly.
Main Methods:
- Literature review of DNA damage response mechanisms.
- Analysis of signaling pathways involved in DDR.
- Focus on protein kinase roles in early DDR events.
Main Results:
- The DDR network involves DNA repair and signal transduction pathways.
- ATM and ATR (Tel1 and Mec1 in yeast) are master regulators of DDR.
- Early DDR steps include DNA lesion recognition and protein complex formation at damage sites.
Conclusions:
- Understanding the early DDR steps is vital for comprehending cellular maintenance.
- The DDR network is essential for preventing diseases associated with DNA damage.
- This review provides insights into the initiating events of the DDR.
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