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● Article:

   Atef Sobhy Iskander

    

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● Insights into DNA Damage Response

   

   Insights, February 2026, Volume 9, Issue 1, 2-41

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Genetic paradigms are exposed to various endogenous and exogenous threats. Organisms have evolved powerful DNA repair mechanisms to cope with these genetic lesions. The MRE-11-RAD50-NBS1 (MRN) complex is a key component for sensing and repairing DNA damage, which activates key regulators of these pathways, namely the ataxia-telangiectasia mutated (ATM) protein and ataxia telangiectasia and Rad3-related protein (ATR). ATM, in turn, activates several downstream effectors, such as checkpoint kinase 2 (CHK2) and p53. Furthermore, the chaperone heat shock protein 90 (Hsp90) is involved in regulating signaling pathways in DNA repair in response to double-strand breaks (DSBs). Overexpression of these essential proteins has devastating consequences and is frequently found in tumor cells. To gain new insights into restriction of these overexpression, this study briefly focuses on the signaling pathways, architectures, and conformational aspects of these proteins. The primary goal of this contribution is to share ideas by proposing hypothetical therapeutic approaches to overcome the abnormal phenotypes resulting from aberrations in these proteins. This may lead to minimizing the accumulation of deleterious mutations due to DNA damage and preserving genome integrity.  
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