ArticleNucleic acids research2022
RNF4 controls the extent of replication fork reversal to preserve genome stability.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- SUMOylation is destined for regulatory T cell-related immune dysregulation.Cell death discovery · 2026Review
- Decoding replication stress responses through post-translational modifications.Nature chemical biology · 2025Review
- Cysteine-reactive covalent chloro-N-acetamide ligands induce ferroptosis mediated cell death.EMBO reports · 2025Article
- Multifaceted roles of SUMO in DNA metabolism.Nucleus (Austin, Tex.) · 2024Review
- Mechanisms and regulation of replication fork reversal.DNA repair · 2024Review
- SUMO and the DNA damage response.Biochemical Society transactions · 2024Review
- RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication.The Journal of clinical investigation · 2024Article
- TFIP11 promotes replication fork reversal to preserve genome stability.Nature communications · 2024Article
- Porcine circovirus type 2 infection promotes the SUMOylation of nucleophosmin-1 to facilitate the viral circular single-stranded DNA replication.PLoS pathogens · 2024Article
- MBD1 protects replication fork stability by recruiting PARP1 and controlling transcription-replication conflicts.Cancer gene therapy · 2024Article
- Review
- BioE3 identifies specific substrates of ubiquitin E3 ligases.Nature communications · 2023Article
- The FLIP-FIGNL1 complex regulates the dissociation of RAD51/DMC1 in homologous recombination and replication fork restart.Nucleic acids research · 2023Article
- RNF4 and USP7 cooperate in ubiquitin-regulated steps of DNA replication.Open biology · 2023Article
- CSF2RB overexpression promotes the protective effects of mesenchymal stromal cells against ischemic heart injury.Theranostics · 2023Article
- Ubiquitin and SUMO pathways in DNA replication and replication-coupled repair.Critical reviews in biochemistry and molecular biologyReview
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replication fork reversal occurs via a two-step process that entails reversal initiation and reversal extension. DNA topoisomerase IIalpha (TOP2A) facilitates extensive fork reversal, on one hand through resolving the topological stress generated by the initial reversal, on the other hand via its role in recruiting the SUMO-targeted DNA translocase PICH to stalled forks in a manner that is dependent on its SUMOylation by the SUMO E3 ligase ZATT. However, how TOP2A activities at stalled forks are precisely regulated remains poorly understood. Here we show that, upon replication stress, the SUMO-targeted ubiquitin E3 ligase RNF4 accumulates at stalled forks and targets SUMOylated TOP2A for ubiquitination and degradation. Downregulation of RNF4 resulted in aberrant activation of the ZATT-TOP2A-PICH complex at stalled forks, which in turn led to excessive reversal and elevated frequencies of fork collapse. These results uncover a previously unidentified regulatory mechanism that regulates TOP2A activities at stalled forks and thus the extent of fork reversal.
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