At the Interface of Three Nucleic Acids: The Role of RNA-Binding Proteins and Poly(ADP-ribose) in DNA Repair.

RNA-binding proteins (RBPs) regulate RNA metabolism, from synthesis to decay. When bound to RNA, RBPs act as guardians of the genome integrity at different levels, from DNA damage prevention to the post-transcriptional regulation of gene expression. Recently, RBPs have been shown to participate in DNA repair. This fact is of special interest as DNA repair pathways do not generally involve RNA. DNA damage in higher organisms triggers the formation of the RNA-like polymer - poly(ADP-ribose) (PAR). Nucleic acid-like properties allow PAR to recruit DNA- and RNA-binding proteins to the site of DNA damage. It is suggested that poly(ADP-ribose) and RBPs not only modulate the activities of DNA repair factors, but that they also play an important role in the formation of transient repairosome complexes in the nucleus. Cytoplasmic biomolecules are subjected to similar sorting during the formation of RNA assemblages by functionally related mRNAs and promiscuous RBPs. The Y-box-binding protein 1 (YB-1) is the major component of cytoplasmic RNA granules. Although YB-1 is a classic RNA-binding protein, it is now regarded as a non-canonical factor of DNA repair.

Y-Box-Binding Protein 1 Stimulates Abasic Site Cleavage.

Apurinic/apyrimidinic (AP) sites are among the most frequent DNA lesions. The first step in the AP site repair involves the magnesium-dependent enzyme AP endonuclease 1 (APE1) that catalyzes hydrolytic cleavage of the DNA phosphodiester bond at the 5' side of the AP site, thereby generating a single-strand DNA break flanked by the 3'-OH and 5'-deoxyribose phosphate (dRP) groups. Increased APE1 activity in cancer cells might correlate with tumor chemoresistance to DNA-damaging treatment. It has been previously shown that the multifunctional oncoprotein Y-box-binding protein 1 (YB-1) interacts with APE1 and inhibits APE1-catalyzed hydrolysis of AP sites in single-stranded DNAs. In this work, we demonstrated that YB-1 stabilizes the APE1 complex with double-stranded DNAs containing the AP sites and stimulates cleavage of these AP sites at low magnesium concentrations.