Literature DB >> 33137198

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

Valentina Riva1, Anna Garbelli1, Federica Casiraghi1, Francesca Arena1, Claudia Immacolata Trivisani2, Assunta Gagliardi3, Luca Bini3, Martina Schroeder4, Antonio Maffia1, Simone Sabbioneda1, Giovanni Maga1.   

Abstract

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.
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Year:  2020        PMID: 33137198      PMCID: PMC7672437          DOI: 10.1093/nar/gkaa948

Source DB:  PubMed          Journal:  Nucleic Acids Res        ISSN: 0305-1048            Impact factor:   16.971


  40 in total

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3.  Semi-supervised learning for peptide identification from shotgun proteomics datasets.

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4.  The overexpression of specialized DNA polymerases in cancer.

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5.  Ribonucleotide triggered DNA damage and RNA-DNA damage responses.

Authors:  Bret D Wallace; R Scott Williams
Journal:  RNA Biol       Date:  2014       Impact factor: 4.652

6.  Measuring the Levels of Ribonucleotides Embedded in Genomic DNA.

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9.  Impact of ribonucleotide incorporation by DNA polymerases β and λ on oxidative base excision repair.

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10.  A hypomorphic inherited pathogenic variant in DDX3X causes male intellectual disability with additional neurodevelopmental and neurodegenerative features.

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  5 in total

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Review 4.  DEAD-Box RNA Helicases DDX3X and DDX5 as Oncogenes or Oncosuppressors: A Network Perspective.

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Review 5.  Targeting the DEAD-Box RNA Helicase eIF4A with Rocaglates-A Pan-Antiviral Strategy for Minimizing the Impact of Future RNA Virus Pandemics.

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  5 in total

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