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PXD021445

PXD021445 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe E3 ubiquitin ligase RFWD3 is required for translesion DNA synthesis (total proteome)
DescriptionLesions on DNA can uncouple DNA synthesis from helicase unwinding, generating stretches of unreplicated single stranded DNA (ssDNA) behind the replication fork. These ssDNA gaps need to be filled in to complete DNA duplication and thereby avoid the generation of DNA double-stranded breaks (DSBs), a major source of genomic instability. Gap filling repair involves either translesion DNA synthesis (TLS) or template switching (TS) to bypass the lesion. At the heart of 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 non-specific ubiquitylation of proteins on ssDNA, to enhance protein accumulation and stimulate gap filling repair. The absence of RFWD3 leads to a profound defect in recruitment of key repair and signaling factors to damaged chromatin, including ubiquitin and proteins known to ubiquitylate and interact with ubiquitylated PCNA. As a result, PCNA ubiquitylation is severely inhibited without RFWD3, and TLS across different DNA lesions drastically impaired. We propose that RFWD3 is an essential coordinator of the response to ssDNA gaps, where it triggers non-specific ubiquitylation to drive recruitment of effectors of PCNA ubiquitylation and DNA damage bypass.
HostingRepositoryPRIDE
AnnounceDate2020-12-15
AnnouncementXMLSubmission_2021-02-11_22:36:02.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterIvo Hendriks
SpeciesList scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-13 23:14:12ID requested
12020-12-15 04:36:15announced
22021-02-11 22:36:03announced2021-02-12: Updated publication reference for PubMed record(s): 33321094.
Publication List
Gallina I, Hendriks IA, Hoffmann S, Larsen NB, Johansen J, Colding-Christensen CS, Schubert L, Sell, é, s-Baiget S, F, á, bi, á, n Z, K, ü, hbacher U, Gao AO, R, ä, schle M, Rasmussen S, Nielsen ML, Mailand N, Duxin JP, The ubiquitin ligase RFWD3 is required for translesion DNA synthesis. Mol Cell, 81(3):442-458.e9(2021) [pubmed]
Keyword List
submitter keyword: RFWD3, CHROMASS, Xenopus, ubiquitin, DNA, damage, TLS, TS, PCNA, total proteome
Contact List
Michael Lund Nielsen
contact affiliationProteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact emailmichael.lund.nielsen@cpr.ku.dk
lab head
Ivo Hendriks
contact affiliationNovo Nordisk Foundation Center for Protein Research, University of Copenhagen
contact emailivo.a.hendriks@gmail.com
dataset submitter
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