Abstract
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.
Highlights
The human genome is constantly exposed to various genotoxic agents that have the potential to damage DNA
DNA ends with by theataxia-telangiectasia combined action of MRNmutated complex and activation; (2) 50 -30 resection of the DNA ends by the combined action of MRN complex and CtIP protein, which results in formation of single-stranded DNA overhangs on both break ends; (3) coverage and stabilization of the ssDNA overhangs by replication protein A (RPA) action; (4) displacement of RPA
BRACs or other homologous recombination (HR) proteins, RAD52 protein can assume a back-up function to ensure damage repair. This RAD52 role is verified in S. cerevisiae, given that, unlike many other eukaryotes, their genome does not encode BRCA1/2 homologs
Summary
Considering that DDR involves the action of multiple proteins responsible for recognition and signaling of DNA damages and consequent repair, a correct coordination of all activated cellular pathways is needed. In this sense, several classes of proteins have been extensively identified, including damage sensors, transducers, mediators, and effectors. An efficient DDR, which correctly repairs damage, can negatively influence the objective of therapy by decreasing tumor cell death [13] This promising strategy of DDR-pathways suppression resulting in an increase in conventional chemotherapeutics efficacy has become an attractive cancer therapeutic approach. A deeper understanding of DNA repair mechanisms may be an essential alternative to achieve a successful cancer therapy
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