ArticleGenes & development2013
RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 107 citations in OpenAlex.
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- TOPBP1-PLK1 interaction preserves genome integrity during mitosis.Nucleic acids research · 2026Article
- RNF4 and USP7 coordinate spatial regulation of SLX4 stability within the PML nuclear bodies.Nucleic acids research · 2025Article
- Multifaceted roles of SUMO in DNA metabolism.Nucleus (Austin, Tex.) · 2024Review
- p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis.Nucleic acids research · 2024Article
- The anti-tumor effect of trifluridine via induction of aberrant mitosis is unaffected by mutations modulating p53 activity.Cell death discovery · 2024Article
- Improved detection of DNA replication fork-associated proteins.Cell reports · 2024Article
- SUMO and the DNA damage response.Biochemical Society transactions · 2024Review
- Poly(ADP-ribosyl)ation of TIMELESS limits DNA replication stress and promotes stalled fork protection.Cell reports · 2024Article
- RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication.The Journal of clinical investigation · 2024Article
- Article
- Comprehensive Characterization of the C3HC4 RING Finger Gene Family in Potato (International journal of molecular sciences · 2024Article
- Mapping combinatorial drug effects to DNA damage response kinase inhibitors.Nature communications · 2023Article
- Review
- ATR inhibition induces synthetic lethality in mismatch repair-deficient cells and augments immunotherapy.Genes & development · 2023Article
- Cyclers' kinases in cell division: from molecules to cancer therapy.Cell death and differentiation · 2023Review
- ATR protects ongoing and newly assembled DNA replication forks through distinct mechanisms.Cell reports · 2023Article
- Emerging strategies for cancer therapy by ATR inhibitors.Cancer science · 2023Review
- The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork.International journal of molecular sciences · 2023Review
- Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The ATR-CHK1 axis stabilizes stalled replication forks and prevents their collapse into DNA double-strand breaks (DSBs). Here, we show that fork collapse in Atr-deleted cells is mediated through the combined effects the sumo targeted E3-ubiquitin ligase RNF4 and activation of the AURKA-PLK1 pathway. As indicated previously, Atr-deleted cells exhibited a decreased ability to restart DNA replication following fork stalling in comparison with control cells. However, suppression of RNF4, AURKA, or PLK1 returned the reinitiation of replication in Atr-deleted cells to near wild-type levels. In RNF4-depleted cells, this rescue directly correlated with the persistence of sumoylation of chromatin-bound factors. Notably, RNF4 repression substantially suppressed the accumulation of DSBs in ATR-deficient cells, and this decrease in breaks was enhanced by concomitant inhibition of PLK1. DSBs resulting from ATR inhibition were also observed to be dependent on the endonuclease scaffold protein SLX4, suggesting that RNF4 and PLK1 either help activate the SLX4 complex or make DNA replication fork structures accessible for subsequent SLX4-dependent cleavage. Thus, replication fork collapse following ATR inhibition is a multistep process that disrupts replisome function and permits cleavage of the replication fork.
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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.