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 |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:81 |
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Enthalten in: |
Molecular cell - 81(2021), 3 vom: 04. Feb., Seite 442-458.e9 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Gallina, Irene [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 24.02.2021 Date Revised 24.02.2021 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.molcel.2020.11.029 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM318862352 |
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100 | 1 | |a Gallina, Irene |e verfasserin |4 aut | |
245 | 1 | 4 | |a The ubiquitin ligase RFWD3 is required for translesion DNA synthesis |
264 | 1 | |c 2021 | |
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500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a CHROMASS | |
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700 | 1 | |a Hendriks, Ivo A |e verfasserin |4 aut | |
700 | 1 | |a Hoffmann, Saskia |e verfasserin |4 aut | |
700 | 1 | |a Larsen, Nicolai B |e verfasserin |4 aut | |
700 | 1 | |a Johansen, Joachim |e verfasserin |4 aut | |
700 | 1 | |a Colding-Christensen, Camilla S |e verfasserin |4 aut | |
700 | 1 | |a Schubert, Lisa |e verfasserin |4 aut | |
700 | 1 | |a Sellés-Baiget, Selene |e verfasserin |4 aut | |
700 | 1 | |a Fábián, Zita |e verfasserin |4 aut | |
700 | 1 | |a Kühbacher, Ulrike |e verfasserin |4 aut | |
700 | 1 | |a Gao, Alan O |e verfasserin |4 aut | |
700 | 1 | |a Räschle, Markus |e verfasserin |4 aut | |
700 | 1 | |a Rasmussen, Simon |e verfasserin |4 aut | |
700 | 1 | |a Nielsen, Michael L |e verfasserin |4 aut | |
700 | 1 | |a Mailand, Niels |e verfasserin |4 aut | |
700 | 1 | |a Duxin, Julien P |e verfasserin |4 aut | |
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