The ubiquitin ligase RFWD3 is required for translesion DNA synthesis

Research output: Contribution to journalJournal articlepeer-review

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The ubiquitin ligase RFWD3 is required for translesion DNA synthesis. / Gallina, Irene; Hendriks, Ivo A; Hoffmann, Saskia; Larsen, Nicolai B; Johansen, Joachim; Colding-Christensen, Camilla S; Schubert, Lisa; Sellés-Baiget, Selene; Fábián, Zita; Kühbacher, Ulrike; Gao, Alan O; Räschle, Markus; Rasmussen, Simon; Nielsen, Michael L; Mailand, Niels; Duxin, Julien P.

In: Molecular Cell, Vol. 81, No. 3, 2021, p. 442-458.e9.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Gallina, I, Hendriks, IA, Hoffmann, S, Larsen, NB, Johansen, J, Colding-Christensen, CS, Schubert, L, Sellés-Baiget, S, Fábián, Z, Kühbacher, U, Gao, AO, Räschle, M, Rasmussen, S, Nielsen, ML, Mailand, N & Duxin, JP 2021, 'The ubiquitin ligase RFWD3 is required for translesion DNA synthesis', Molecular Cell, vol. 81, no. 3, pp. 442-458.e9. https://doi.org/10.1016/j.molcel.2020.11.029

APA

Gallina, I., Hendriks, I. A., Hoffmann, S., Larsen, N. B., Johansen, J., Colding-Christensen, C. S., Schubert, L., Sellés-Baiget, S., Fábián, Z., Kühbacher, U., Gao, A. O., Räschle, M., Rasmussen, S., Nielsen, M. L., Mailand, N., & Duxin, J. P. (2021). The ubiquitin ligase RFWD3 is required for translesion DNA synthesis. Molecular Cell, 81(3), 442-458.e9. https://doi.org/10.1016/j.molcel.2020.11.029

Vancouver

Gallina I, Hendriks IA, Hoffmann S, Larsen NB, Johansen J, Colding-Christensen CS et al. The ubiquitin ligase RFWD3 is required for translesion DNA synthesis. Molecular Cell. 2021;81(3):442-458.e9. https://doi.org/10.1016/j.molcel.2020.11.029

Author

Gallina, Irene ; Hendriks, Ivo A ; Hoffmann, Saskia ; Larsen, Nicolai B ; Johansen, Joachim ; Colding-Christensen, Camilla S ; Schubert, Lisa ; Sellés-Baiget, Selene ; Fábián, Zita ; Kühbacher, Ulrike ; Gao, Alan O ; Räschle, Markus ; Rasmussen, Simon ; Nielsen, Michael L ; Mailand, Niels ; Duxin, Julien P. / The ubiquitin ligase RFWD3 is required for translesion DNA synthesis. In: Molecular Cell. 2021 ; Vol. 81, No. 3. pp. 442-458.e9.

Bibtex

@article{7872d3733f1a47ccab37e1a489410938,
title = "The ubiquitin ligase RFWD3 is required for translesion DNA synthesis",
abstract = "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.",
keywords = "Animals, Cell Line, Tumor, Chromatin/genetics, DNA Breaks, Single-Stranded, DNA Repair, DNA Replication, DNA-Directed DNA Polymerase/metabolism, Female, Humans, Proliferating Cell Nuclear Antigen/genetics, Substrate Specificity, Ubiquitin-Protein Ligases/genetics, Ubiquitination, Xenopus laevis",
author = "Irene Gallina and Hendriks, {Ivo A} and Saskia Hoffmann and Larsen, {Nicolai B} and Joachim Johansen and Colding-Christensen, {Camilla S} and Lisa Schubert and Selene Sell{\'e}s-Baiget and Zita F{\'a}bi{\'a}n and Ulrike K{\"u}hbacher and Gao, {Alan O} and Markus R{\"a}schle and Simon Rasmussen and Nielsen, {Michael L} and Niels Mailand and Duxin, {Julien P}",
year = "2021",
doi = "10.1016/j.molcel.2020.11.029",
language = "English",
volume = "81",
pages = "442--458.e9",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - The ubiquitin ligase RFWD3 is required for translesion DNA synthesis

AU - Gallina, Irene

AU - Hendriks, Ivo A

AU - Hoffmann, Saskia

AU - Larsen, Nicolai B

AU - Johansen, Joachim

AU - Colding-Christensen, Camilla S

AU - Schubert, Lisa

AU - Sellés-Baiget, Selene

AU - Fábián, Zita

AU - Kühbacher, Ulrike

AU - Gao, Alan O

AU - Räschle, Markus

AU - Rasmussen, Simon

AU - Nielsen, Michael L

AU - Mailand, Niels

AU - Duxin, Julien P

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line, Tumor

KW - Chromatin/genetics

KW - DNA Breaks, Single-Stranded

KW - DNA Repair

KW - DNA Replication

KW - DNA-Directed DNA Polymerase/metabolism

KW - Female

KW - Humans

KW - Proliferating Cell Nuclear Antigen/genetics

KW - Substrate Specificity

KW - Ubiquitin-Protein Ligases/genetics

KW - Ubiquitination

KW - Xenopus laevis

U2 - 10.1016/j.molcel.2020.11.029

DO - 10.1016/j.molcel.2020.11.029

M3 - Journal article

C2 - 33321094

VL - 81

SP - 442-458.e9

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 3

ER -

ID: 257368171