The ubiquitin ligase RFWD3 is required for translesion DNA synthesis
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
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.
I: Molecular Cell, Bind 81, Nr. 3, 2021, s. 442-458.e9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
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