Non-coding RNAs in DNA damage and repair

Abstract

Non-coding RNAs (ncRNAs) are increasingly recognized as central players in diverse biological processes. Upon DNA damage, the DNA damage response (DDR) elicits a complex signaling cascade, which includes the induction of multiple ncRNA species. Recent studies indicate that DNA-damage induced ncRNAs contribute to regulation of cell cycle, apoptosis and DNA repair, and thus play a key role in maintaining genome stability. This review summarizes the emerging role of ncRNAs in DNA damage and repair.

Figure 1

The complex interplay of ncRNAs and DNA Damage. Activation of the DNA Damage Response (DDR) induces multiple kinds of noncoding RNAs (ncRNAs) such as microRNAs (miRNAs), DROSHA and DICER dependent (ddRNAs), DSB-induced small RNAS (diRNAs), and long intergenic noncoding RNAs (lincRNAs). ATM, BRCA1 and p53 are involved in regulation of miRNA biogenesis. P53 and BRCA1 also regulate miRNA expression. Misregulated miRNAs expression such as in cancer may also contribute to direct inhibition of key proteins in DDR such as ATM, DNAPKcs, H2AX, BRCA1 and p53. DDRNAs produced from sites of DNA damage contribute to formation of DNA repair foci. diRNAs contribute to (Homologous Recombination) HR mediated repair. p53 also induces expression of lincRNAs which modulate gene expression to regulate cell cycle and apoptosis. Activating effects (green), inhibitory effects (red).