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Each cell of our body receives tens-of-thousands of DNA lesions per day due to a variety of internal and environmental factors. These lesions, if not properly repaired, can lead to mutations and wider-scale genome aberrations that threaten cell viability and might ultimately result in cancer. To counter this threat, life has evolved systems, collectively called the DNA damage response, to detect DNA damage, signal it's presence and mediate it's repair. DNA repair is crucial in many biological processes including the development of the immune system, meiotic recombination and prevent diverse human diseases. Inherited DNA repair defects can be catastrophic, causing developmental abnormalities, heightened cancer predisposition, immune-deficiency, neurodegenerative disease, and premature ageing.
There are different types of DNA damage and therefore different molecular pathways of DNA repair to correct them, including non-homologous end joining, homologous recombination, mismatch repair and nucleotide excision repair. Numerous proteins and pathways have been involved in these processes. The ATM and ATR kinases, as well as DNA-PK, are key for detection of the DNA lesions. Chromatin remodelers participate in making sure that the chromatin environment is accessible to the DNA repair apparatus, and key repair factors such as RPA, Rad51 and the fanconi anemia proteins directly act in repairing the DNA lesions. Importantly the p53 network, the RAS GTPase superfamily, and the ubiquitin system are also involved in different aspects of the DNA damage response.
Antibodies are a common tool for studying the DNA damage response, allowing to measure the expression and activation of key proteins in these processes as well as their post-translational modifications, such as the phosphorylation of H2A.X, a hallmark of DNA damage activation. Importantly, antibodies are also widely used to determine their cellular localization and the choreography of their recruitment to the damaged DNA.
Development of antibodies to the latest discovered targets in the DNA damage response and new tools to study these pathways will not only enhance our knowledge on the topic, but will also present exciting opportunities for better understanding human health and disease.
DNA repair is crucial to an organism's ability to maintain its genome integrity and thus its function. Various pathways of DNA repair exist including:
Article written by Dr Ilaria Guerini
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