The role of RAD52 gene in genomic integrity maintenance and its potential as a therapeutic target

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The role of RAD52 gene in genomic integrity maintenance and its potential as a therapeutic target

Monday, 30.12.2019

DNA damage signaling pathways, including DNA repair machinery, are essential to genomic stability maintenance, growth suppression of cells with genetic defects and, consequently in carcinogenesis prevention. On the other hand, the treatment outcome is highly influenced by all cellular processes involved in DNA damage reponse (DDR). Therefore, a therapeutic strategy that targets tumor-specific DNA repair pathways through RAD52 gene activity inactivation may be a promising approach to improve therapy efficacy since it can result in an increased tumor cells sensitization to cell death and a decreased toxicity to normal cells. New approaches of RAD52 inhibition would potentially provide a complementary strategy for targeting BRCA-deficient cancers in addition to PARP inhibitors.


Authors and Affiliations:

Augusto Nogueira1,2, Mara Fernandes1,2, Raquel Catarino1 and Rui Medeiros1,2,3,4

Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto, 4200-072 Porto, Portugal.

Faculty of Medicine of University of Porto (FMUP), 4200-319 Porto, Portugal.

Biomedical Research Center (CEBIMED), Faculty of Health Sciences of Fernando Pessoa University, 4249-004 Porto, Portugal.

Research Department, Portuguese League against Cancer (NRNorte), 4200-172 Porto, Portugal.



Genomes are continually subjected to DNA damage whether they are induced from intrinsic physiological processes or extrinsic agents. Double-stranded breaks (DSBs) are the most injurious type of DNA damage, being induced by ionizing radiation (IR) and cytotoxic agents used in cancer treatment. The failure to repair DSBs can result in aberrant chromosomal abnormalities which lead to cancer development. An intricate network of DNA damage signaling pathways is usually activated to eliminate these damages and to restore genomic stability. These signaling pathways include the activation of cell cycle checkpoints, DNA repair mechanisms, and apoptosis induction, also known as DNA damage response (DDR)-mechanisms. Remarkably, the homologous recombination (HR) is the major DSBs repairing pathway, in which RAD52 gene has a crucial repairing role by promoting the annealing of complementary single-stranded DNA and by stimulating RAD51 recombinase activity. Evidence suggests that variations in RAD52 expression can influence HR activity and, subsequently, influence the predisposition and treatment efficacy of cancer. In this review, we present several reports in which the down or upregulation of RAD52 seems to be associated with different carcinogenic processes. In addition, we discuss RAD52 inhibition in DDR-defective cancers as a possible target to improve cancer therapy efficacy.


Journal: Cancers (Basel)