AI Article Synopsis
- DNA double-strand breaks (DSBs) are serious genomic damage that can lead to cancer and affect immune development, making their repair pathways essential.
- A new method combining ribonuclease and detergent pre-extraction with high-resolution microscopy allows for the visualization of key repair factors like the DSB sensor Ku at various DSB types, including those caused by cancer treatments.
- This innovative approach enhances our understanding of DNA repair mechanisms, helps identify how cells choose their repair pathways, and assesses cellular responses to anticancer drugs.
Article Abstract
DNA double-strand breaks (DSBs) are the most toxic of all genomic insults, and pathways dealing with their signaling and repair are crucial to prevent cancer and for immune system development. Despite intense investigations, our knowledge of these pathways has been technically limited by our inability to detect the main repair factors at DSBs in cells. In this paper, we present an original method that involves a combination of ribonuclease- and detergent-based preextraction with high-resolution microscopy. This method allows direct visualization of previously hidden repair complexes, including the main DSB sensor Ku, at virtually any type of DSB, including those induced by anticancer agents. We demonstrate its broad range of applications by coupling it to laser microirradiation, super-resolution microscopy, and single-molecule counting to investigate the spatial organization and composition of repair factories. Furthermore, we use our method to monitor DNA repair and identify mechanisms of repair pathway choice, and we show its utility in defining cellular sensitivities and resistance mechanisms to anticancer agents.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3734090 | PMC |
| http://dx.doi.org/10.1083/jcb.201303073 | DOI Listing |
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