The ubiquitin ligase RFWD3 is required for translesion DNA synthesis

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved..

Lesions on DNA uncouple DNA synthesis from the replisome, generating stretches of unreplicated single-stranded DNA (ssDNA) behind the replication fork. These ssDNA gaps need to be filled in to complete DNA duplication. Gap-filling synthesis involves either translesion DNA synthesis (TLS) or template switching (TS). Controlling these processes, ubiquitylated PCNA recruits many proteins that dictate pathway choice, but the enzymes regulating PCNA ubiquitylation in vertebrates remain poorly defined. Here we report that the E3 ubiquitin ligase RFWD3 promotes ubiquitylation of proteins on ssDNA. The absence of RFWD3 leads to a profound defect in recruitment of key repair and signaling factors to damaged chromatin. As a result, PCNA ubiquitylation is inhibited without RFWD3, and TLS across different DNA lesions is drastically impaired. We propose that RFWD3 is an essential coordinator of the response to ssDNA gaps, where it promotes ubiquitylation to drive recruitment of effectors of PCNA ubiquitylation and DNA damage bypass.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:81

Enthalten in:

Molecular cell - 81(2021), 3 vom: 04. Feb., Seite 442-458.e9

Sprache:

Englisch

Beteiligte Personen:

Gallina, Irene [VerfasserIn]
Hendriks, Ivo A [VerfasserIn]
Hoffmann, Saskia [VerfasserIn]
Larsen, Nicolai B [VerfasserIn]
Johansen, Joachim [VerfasserIn]
Colding-Christensen, Camilla S [VerfasserIn]
Schubert, Lisa [VerfasserIn]
Sellés-Baiget, Selene [VerfasserIn]
Fábián, Zita [VerfasserIn]
Kühbacher, Ulrike [VerfasserIn]
Gao, Alan O [VerfasserIn]
Räschle, Markus [VerfasserIn]
Rasmussen, Simon [VerfasserIn]
Nielsen, Michael L [VerfasserIn]
Mailand, Niels [VerfasserIn]
Duxin, Julien P [VerfasserIn]

Links:

Volltext

Themen:

Anemia
CHROMASS
Chromatin
DNA-Directed DNA Polymerase
DPC repair
EC 2.3.2.27
EC 2.7.7.7
HMCES
ICL repair
Journal Article
PCNA
PCNA protein, human
Proliferating Cell Nuclear Antigen
RFWD3
RFWD3 protein, human
Research Support, Non-U.S. Gov't
TLS
UV lesions
Ubiquitin-Protein Ligases
Ubiquitylation

Anmerkungen:

Date Completed 24.02.2021

Date Revised 24.02.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.molcel.2020.11.029

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM318862352