Novel alternative ribonucleotide excision repair pathways in human cells by DDX3X and specialized DNA polymerases.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 11 2020
18 11 2020
Historique:
accepted:
08
10
2020
revised:
02
10
2020
received:
21
01
2020
pubmed:
3
11
2020
medline:
4
2
2021
entrez:
2
11
2020
Statut:
ppublish
Résumé
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) δ or ϵ, 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 δ but also with the repair Pols β and λ. 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.
Identifiants
pubmed: 33137198
pii: 5952198
doi: 10.1093/nar/gkaa948
pmc: PMC7672437
doi:
Substances chimiques
Ribonucleotides
0
Adenosine Triphosphate
8L70Q75FXE
DNA polymerase beta2
EC 2.7.7.-
DNA Polymerase beta
EC 2.7.7.7
ribonuclease HII
EC 3.1.26.-
Ribonuclease H
EC 3.1.26.4
DDX3X protein, human
EC 3.6.1.-
DEAD-box RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11551-11565Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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