Dual roles of DNA repair enzymes in RNA biology/post‐transcriptional control

Abstract

Despite consistent research into the molecular principles of the DNA damage repair pathway for almost two decades, it has only recently been found that RNA metabolism is very tightly related to this pathway, and the two ancient biochemical mechanisms act in alliance to maintain cellular genomic integrity. The close links between these pathways are well exemplified by examining the base excision repair pathway, which is now well known for dual roles of many of its members in DNA repair and RNA surveillance, including APE1, SMUG1, and PARP1. With additional links between these pathways steadily emerging, this review aims to provide a summary of the emerging roles for DNA repair proteins in the post-transcriptional regulation of RNAs. WIREs RNA 2016, 7:604-619. doi: 10.1002/wrna.1353 For further resources related to this article, please visit the WIREs website.

Unveiling the non-repair face of the Base Excision Repair pathway in RNA processing: A missing link between DNA repair and gene expression?

“…Actually, the major focus is on APE1, SMUG1 and PARP1, as prototypical examples [17,59,[62][63][64]. In this review, in particular, we highlight current knowledge of APE1 in controlling RNA metabolism.…”

“…Moreover, despite the previous consistent research into APE1 molecular mechanisms in DNA damage repair, only recently it has been hypothesized that this protein may play an unsuspected though important function in RNA metabolism impacting on the post-transcriptional control of gene expression [17,58,59]. Overall, these pioneering studies hold the promise to change the focus of scientific research from investigating the canonical roles of BER enzymes in DNA repair to the study of their function in gene regulation highlighting the BER peculiarity for eukaryotic cells.…”

“…In addition, ncRNAs and miRNAs act at multiple levels of DNA damage response regulation and have been proposed as novel anticancer therapeutic targets [59]. DNA repair enzymes, in particular a large cohort of BER proteins, have been implicated in RNA metabolism and in transcriptional regulation of genes suggesting that DNA damage repair and RNA pathways are tightly inter-regulated [59].…”

RNA G-quadruplexes: emerging mechanisms in disease

“…Such a functional interplay could have important function in preserving genomic stability. Indeed, recent studies show that protein factors with a dual function in both biochemical processes play a critical role in maintaining cellular genomic integrity (115,116) and that DNA/RNA G4s contribute to genome instability by regulating both DNA-related processes (46) and RNA-based gene expression mechanisms (50). …”

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

“…Base excision repair (BER) provides a clear picture of DNA repair and RNA metabolism coupling, since numerous molecules of this pathway, including APE1, SMUG1 and PARP1, are involved in RNA metabolism [1]. Obviously, transcription factors can mediate DNA repair by regulating the expression of repair enzymes [2].…”