CNR ExploRA

Articolo in rivista, 2020, ENG, 10.1093/nar/gkaa948

Novel alternative ribonucleotide excision repair pathways in human cells by DDX3X and specialized DNA polymerases

Riva V, Garbelli A, Casiraghi F, Arena F, Trivisani CI, Gagliardi A, Bini L, Schroeder M, Maffia A, Sabbioneda S, Maga G.

Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', via Abbiategrasso 207, Pavia, I-27100, , Italy; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. De Gasperi 2, Siena, I-53100, , Italy; Department of Life Sciences, University of Siena, Via A. Moro 2, Siena, I-53100, , Italy; Kathleen Lonsdale Institute for Human Health Research, Biology Department, Maynooth University, Co. Kildare, Maynooth, , Ireland

Removal of ribonucleotides (rNMPs) incorporated into the genome by the ribonucleotide excision repair (RER) is essential to avoid genetic instability. In eukaryotes, the RNaseH2 is the only known enzyme able to incise 5' of the rNMP, starting the RER process, which is subsequently carried out by replicative DNA polymerases (Pols) ? or ?, together with Flap endonuclease 1 (Fen-1) and DNA ligase 1. Here, we show that the DEAD-box RNA helicase DDX3X has RNaseH2-like activity and can support fully reconstituted in vitro RER reactions, not only with Pol ? but also with the repair Pols ? and ?. Silencing of DDX3X causes accumulation of rNMPs in the cellular genome. These results support the existence of alternative RER pathways conferring high flexibility to human cells in responding to the threat posed by rNMPs incorporation.

Nucleic acids research (Online) 48 (20), pp. 11551–11565