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The ATR barrier to replication-born DNA damage.
Andrés J López-Contreras1, Oscar Fernandez-Capetillo
1Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), 3 Melchor Fernandez Almagro Street, Madrid E-28029, Spain. ajlopez@cnio.es
DNA Repair
|November 2, 2010
Summary
Replicative stress, involving single-stranded DNA (ssDNA), triggers a cellular response coordinated by ATR kinase. This review explores the connection between ATR, ageing, and cancer.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- DNA duplication can lead to abnormalities known as replicative stress (RS).
- Replicative stress involves unprotected single-stranded DNA (ssDNA) regions.
- ssDNA is also found at DNA double-strand breaks (DSBs).
Purpose of the Study:
- To review the cellular response to ssDNA intermediates.
- To discuss the role of ATR (ATM and Rad3-related) kinase in this response.
- To explore the connection between ATR, ageing, and cancer.
Main Methods:
- Literature review of findings connecting ATR to ageing and cancer.
- Discussion of the phosphorylation-based signaling cascade initiated by ATR activation.
Main Results:
- ATR kinase activation coordinates the cellular response to ssDNA.
- ATR is essential for replicating cells.
- Defective ATR response has implications for mammalian organisms.
Conclusions:
- ATR plays a critical role in managing DNA damage.
- Understanding ATR's function is crucial for insights into ageing and cancer development.
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Overview