ArticlePLoS biology2024
SMARCAL1 ubiquitylation controls its association with RPA-coated ssDNA and promotes replication fork stability.
Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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Who cites it
12 citing papers in PubMed, 10 citations in OpenAlex.
- DPP9 modulates RPA1 stability and temozolomide sensitivity through RFWD3 Nuclear localization in glioma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Comprehensive genomics and functional analyses identifyTranslational cancer research · 2026Article
- A Landscape Analysis of Human SUMOylation.Molecular & cellular proteomics : MCP · 2026Article
- Replication protein A protects lagging strand gaps, restricting PARP inhibitor-induced synthetic lethality in BRCA1-deficient tumors.Nucleic acids research · 2026Article
- SLFN11 counteracts the RFWD3-PRIMPOL DNA damage tolerance axis to restrain gapped DNA synthesis in response to replication stress.Nature communications · 2025Article
- Ubiquitination of the histone variant mH2A1.2 prevents toxic RAD18 accumulation at a subset of genomic loci upon replication stress.Molecular cell · 2025Article
- Estrogen Promotes Endometrial Cancer Development by Modulating ZNF626, SLK, and RFWD3 Gene Expression and Inducing Immune Inflammatory Changes.Biomedicines · 2025Article
- HeterozygousGenes & development · 2024Article
- Mechanisms and regulation of replication fork reversal.DNA repair · 2024Review
- An E3 ubiquitin ligase localization screen uncovers DTX2 as a novel ADP-ribosylation-dependent regulator of DNA double-strand break repair.The Journal of biological chemistry · 2024Article
- RFWD3: A pivotal E3 ubiquitin ligase in DNA damage response, non-neoplastic disorders and multi-system tumorigenesis.Science progressReview
- Ubiquitin and SUMO pathways in DNA replication and replication-coupled repair.Critical reviews in biochemistry and molecular biologyReview
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Impediments in replication fork progression cause genomic instability, mutagenesis, and severe pathologies. At stalled forks, RPA-coated single-stranded DNA (ssDNA) activates the ATR kinase and directs fork remodeling, 2 key early events of the replication stress response. RFWD3, a recently described Fanconi anemia (FA) ubiquitin ligase, associates with RPA and promotes its ubiquitylation, facilitating late steps of homologous recombination (HR). Intriguingly, RFWD3 also regulates fork progression, restart and stability via poorly understood mechanisms. Here, we used proteomics to identify putative RFWD3 substrates during replication stress in human cells. We show that RFWD3 interacts with and ubiquitylates the SMARCAL1 DNA translocase directly in vitro and following DNA damage in vivo. SMARCAL1 ubiquitylation does not trigger its subsequent proteasomal degradation but instead disengages it from RPA thereby regulating its function at replication forks. Proper regulation of SMARCAL1 by RFWD3 at stalled forks protects them from excessive MUS81-mediated cleavage in response to UV irradiation, thereby limiting DNA replication stress. Collectively, our results identify RFWD3-mediated SMARCAL1 ubiquitylation as a novel mechanism that modulates fork remodeling to avoid genome instability triggered by aberrant fork processing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.