Journal
NUCLEIC ACIDS RESEARCH
Volume 48, Issue 20, Pages 11551-11565Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa948
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Funding
- Italian Association for Cancer Research (AIRC) [IG2017-20762]
- University of Pavia [3237/2017]
- Associazione Italiana per la Ricerca sul Cancro [IG2017-20762]
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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] .
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