Role of Rad51 and DNA repair in cancer: A molecular perspective

Author: Laurini, Erik; Marson, Domenico; Fermeglia, Alice; Aulic, Suzana; Fermeglia, Maurizio; Pricl, Sabrina

Description: The maintenance of genome integrity is essential for any organism survival and for the inheritance of traits to offspring. To the purpose, cells have developed a complex DNA repair system to defend the genetic information against both endogenous and exogenous sources of damage. Accordingly, multiple repair pathways can be aroused from the diverse forms of DNA lesions, which can be effective per se or via crosstalk with others to complete the whole DNA repair process. Deficiencies in DNA healing resulting in faulty repair and/or prolonged DNA damage can lead to genes mutations, chromosome rearrangements, genomic instability, and finally carcinogenesis and/or cancer progression. Although it might seem paradoxical, at the same time such defects in DNA repair pathways may have therapeutic implications for potential clinical practice. Here we provide an overview of the main DNA repair pathways, with special focus on the role played by homologous repair and the RAD51 recombinase protein in the cellular DNA damage response. We next discuss the recombinase structure and function per se and in combination with all its principal mediators and regulators. Finally, we conclude with an analysis of the manifold roles that RAD51 plays in carcinogenesis, cancer progression and anticancer drug resistance, and conclude this work with a survey of the most promising therapeutic strategies aimed at targeting RAD51 in experimental oncology.

Subject headings: Cancer; DNA damage; DNA repair; Homologous recombination; Rad51

Publication year: 2020

Journal or book title: Pharmacology & Therapeutics

Volume: 208

Pages: 107492

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Serial number: 3201

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