Riva, Valentina and Garbelli, Anna and Casiraghi, Federica and Arena, Francesca and Trivisani, Claudia Immacolata and Gagliardi, Assunta and Bini, Luca and Schroeder, Martina and Maffia, Antonio and Sabbioneda, Simone and Maga, Giovanni (2020) Novel alternative ribonucleotide excision repair pathways in human cells by DDX3X and specialized DNA polymerases. Nucleic Acids Research, 48 (20). pp. 11551-11565. ISSN 0305-1048

Preview

Download (3MB) | Preview

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.

Item Type:	Article
Additional Information:	The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors. Present addresses: Federica Casiraghi, CIBIO, Department of Cellular, Computational and Integrative Biology University of Trento, Via Sommarive 9, I-38123 Povo (TN), Italy. Antonio Maffia, University of California Berkeley, Department of Molecular and Cell Biology, Berkeley, CA 94720, USA. ©The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited
Keywords:	Novel; alternative; ribonucleotide; excision repair; pathways; human cells; DDX3X; specialized; DNA polymerases;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	14960
Identification Number:	https://doi.org/10.1093/nar/gkaa948
Depositing User:	Martina Schroeder
Date Deposited:	26 Oct 2021 15:29
Journal or Publication Title:	Nucleic Acids Research
Publisher:	Oxford University Press
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

Repository Staff Only(login required)

Item control page

Downloads

Origin of downloads