DNA repair proteins and other cellular proteins

DNA repair proteins and other cellular proteins refers to a broad and heterogeneous group of molecular entities responsible for maintaining genomic integrity and executing essential cellular functions. This group includes key enzymes in the DNA damage response (DDR) pathway, such as Poly [ADP-ribose] polymerase (PARP), Ataxia telangiectasia mutated (ATM), and Ataxia telangiectasia and Rad3-related (ATR) kinases [O'Connor, Mol Cell 2015]. These proteins are frequently targeted in cancer therapy to exploit vulnerabilities like homologous recombination deficiency, a concept known as synthetic lethality [Lord & Ashworth, Nature 2012]. Beyond specific repair enzymes, this designation often encompasses various cellular proteins that are non-specifically modified by cytotoxic agents like alkylating drugs and platinum complexes [NIH NCI]. These interactions can disrupt protein function, interfere with DNA-protein complexes, and ultimately trigger programmed cell death in rapidly dividing cancer cells [Pearl et al., Nat Rev Cancer 2015]. While targeting these proteins is a cornerstone of modern oncology, the broad nature of these interactions often leads to significant systemic toxicities, such as bone marrow suppression and potential organ damage. Understanding the specific roles of these proteins continues to drive the development of more selective inhibitors aimed at improving the therapeutic index of cancer treatments.

Other names

DNA damage response proteinsDDR proteinsDNA repair enzymesCellular repair machinery

Inhibition of DNA repair pathways (e.g., PARP inhibition) or direct covalent modification of proteins and DNA to induce genomic instability and apoptosis [O'Connor, Mol Cell 2015; NIH NCI].