Peer-Reviewed Journal Details
Mandatory Fields
Riva, V;Garbelli, A;Casiraghi, F;Arena, F;Trivisani, CI;Gagliardi, A;Bini, L;Schroeder, M;Maffia, A;Sabbioneda, S;Maga, G
2020
November
Nucleic Acids Research
Novel alternative ribonucleotide excision repair pathways in human cells by DDX3X and specialized DNA polymerases
Published
0 ()
Optional Fields
STATISTICAL-MODEL BOX ROLES IDENTIFICATION PROTEINS
48
11551
11565
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) delta or epsilon, 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 delta but also with the repair Pols beta and lambda. 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.[GRAPHICS].
OXFORD
0305-1048
10.1093/nar/gkaa948
Grant Details