Human nuclear ARGONAUTE 2 interacts <i>in vivo</i> only with small RNAs and not with DNA

Gioia, Ubaldo; Fagagna, Fabrizio d’Adda di

doi:10.1080/15384101.2015.1044171

Cited by 2 publications

(1 citation statement)

References 18 publications

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“…Moreover, the participation of key downstream effectors in the RNAi pathway, namely the Argonautes, is also contested. 8, 10, 11, 21 Currently, the mechanism by which the diRNAs directly influence repair outcome is under extensive investigation. Nevertheless, it has been reported that in Drosophila cells, these small RNAs can serve as endo-siRNAs to suppress existing transcripts arisen from the portion of DNA harbouring the DSB, as was proposed in N. crassa .…”

Section: An Unlikely Match: Rna Biogenesis Machinery Meets Dna Repairmentioning

confidence: 99%

The emerging role of RNAs in DNA damage repair

Hawley

Wilczynska

et al. 2017

Cell Death Differ

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Many surveillance and repair mechanisms exist to maintain the integrity of our genome. All of the pathways described to date are controlled exclusively by proteins, which through their enzymatic activities identify breaks, propagate the damage signal, recruit further protein factors and ultimately resolve the break with little to no loss of genetic information. RNA is known to have an integral role in many cellular pathways, but, until very recently, was not considered to take part in the DNA repair process. Several reports demonstrated a conserved critical role for RNA-processing enzymes and RNA molecules in DNA repair, but the biogenesis of these damage-related RNAs and their mechanisms of action remain unknown. We will explore how these new findings challenge the idea of proteins being the sole participants in the response to DNA damage and reveal a new and exciting aspect of both DNA repair and RNA biology. Cell Death and Differentiation (2017) 24, 580-587; doi:10.1038/cdd.2017; published online 24 February 2017 FactsThe miRNA biogenesis machinery has a role in DNA damage repair outside of canonical miRNA-mediated translational repression. RNA molecules have been observed in the proximity of DNA breaks and have been implicated in the DNA repair response. These phenomena have been observed in many species, indicating an evolutionarily conserved mechanism. Open QuestionsWhat is the precise role of the RNA-processing enzymes in DNA repair? Do small RNAs have a direct mechanistic role in DNA repair, or do they serve as a by-product of a different RNA species? Is transcription induced locally at sites of DNA damage? Are proximal dormant promoter elements involved, or is an open-ended break sufficient for polymerase recruitment? Can these results be replicated outside of integrated exogenous reporter systems?An Unlikely Match: RNA Biogenesis Machinery Meets DNA Repair Our DNA is constantly exposed to various environmental and chemical agents, including ionising radiation (IR) from cosmic radiation, ultraviolet (UV) light from the sun or even nucleophilic attack induced by chemical compounds in food.1 In fact, DNA damage is intrinsic to the process of life: it is inevitable during replication and essential during meiotic recombination. Also, controlled DNA breaks by topoisomerase occur to facilitate the resolution of supercoiled chromatin structures.Complex mechanisms have evolved to counteract the variety and quantity of DNA damage encountered daily. Generally, DNA damage response (DDR) involves a complex signalling cascade initiated by one of three PI3K-like kinases: ATM, ATR or DNA-PK. They serve to facilitate chromatin modification and remodelling, allowing access to and acting as scaffolds for proteins involved in repair, as well as propagating the damage signal.1 Many of these recruited factors are involved in a binary decision-making process (see Figure 1). The repair of double-strand breaks (DSBs) is resolved by two distinct mechanisms: error-free homologous recombination (HR) or error-prone non-homologous ...

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Section: An Unlikely Match: Rna Biogenesis Machinery Meets Dna Repairmentioning

confidence: 99%

The emerging role of RNAs in DNA damage repair

Hawley

Wilczynska

et al. 2017

Cell Death Differ

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Small RNA-mediated repair of UV-induced DNA lesions by the DNA DAMAGE-BINDING PROTEIN 2 and ARGONAUTE 1

Schalk

Cognat

Graindorge

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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As photosynthetic organisms, plants need to prevent irreversible UV-induced DNA lesions. Through an unbiased, genome-wide approach, we have uncovered a previously unrecognized interplay between Global Genome Repair and small interfering RNAs (siRNAs) in the recognition of DNA photoproducts, prevalently in intergenic regions. Genetic and biochemical approaches indicate that, upon UV irradiation, the DNA DAMAGE-BINDING PROTEIN 2 (DDB2) and ARGONAUTE 1 (AGO1) of Arabidopsis thaliana form a chromatin-bound complex together with 21-nt siRNAs, which likely facilitates recognition of DNA damages in an RNA/DNA complementary strand-specific manner. The biogenesis of photoproduct-associated siRNAs involves the noncanonical, concerted action of RNA POLYMERASE IV, RNA-DEPENDENT RNA POLYMERASE-2, and DICER-LIKE-4. Furthermore, the chromatin association/dissociation of the DDB2-AGO1 complex is under the control of siRNA abundance and DNA damage signaling. These findings reveal unexpected nuclear functions for DCL4 and AGO1, and shed light on the interplay between small RNAs and DNA repair recognition factors at damaged sites.

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Human nuclear ARGONAUTE 2 interacts in vivo only with small RNAs and not with DNA

Cited by 2 publications

References 18 publications

The emerging role of RNAs in DNA damage repair

The emerging role of RNAs in DNA damage repair

Small RNA-mediated repair of UV-induced DNA lesions by the DNA DAMAGE-BINDING PROTEIN 2 and ARGONAUTE 1

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