ArticleThe Journal of cell biology2021
SLX4-XPF mediates DNA damage responses to replication stress induced by DNA-protein interactions.
Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Phosphorylation by CDK1 switches the function of the human SLX4 SAP domain from DNA binding to MUS81 binding.Nucleic acids research · 2026Article
- Synthetic Lethality-Based Targets and Their Exploration in Tumour Combination Strategies.Journal of cellular and molecular medicine · 2025Review
- A genome-wide screen identifies SCAI as a modulator of the UV-induced replicative stress response.PLoS biology · 2022Article
- Microscopic Detection of DNA Synthesis in Early Mitosis at RepetitiveBio-protocol · 2022Article
- Fanconi anemia and dyskeratosis congenita/telomere biology disorders: Two inherited bone marrow failure syndromes with genomic instability.Frontiers in oncology · 2022Review
- Locus-Specific Analysis of Replication Dynamics and Detection of DNA-RNA Hybrids by Immuno Electron Microscopy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- TRF2-mediated ORC recruitment underlies telomere stability upon DNA replication stress.Nucleic acids research · 2021Article
- DNA damage responses that enhance resilience to replication stress.Cellular and molecular life sciences : CMLS · 2021Review
- PHF8-promoted TOPBP1 demethylation drives ATR activation and preserves genome stability.Science advances · 2021Article
- Approaching Protein Barriers: Emerging Mechanisms of Replication Pausing in Eukaryotes.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The DNA damage response (DDR) has a critical role in the maintenance of genomic integrity during chromosome replication. However, responses to replication stress evoked by tight DNA-protein complexes have not been fully elucidated. Here, we used bacterial LacI protein binding to lacO arrays to make site-specific replication fork barriers on the human chromosome. These barriers induced the accumulation of single-stranded DNA (ssDNA) and various DDR proteins at the lacO site. SLX4-XPF functioned as an upstream factor for the accumulation of DDR proteins, and consequently, ATR and FANCD2 were interdependently recruited. Moreover, LacI binding in S phase caused underreplication and abnormal mitotic segregation of the lacO arrays. Finally, we show that the SLX4-ATR axis represses the anaphase abnormality induced by LacI binding. Our results outline a long-term process by which human cells manage nucleoprotein obstacles ahead of the replication fork to prevent chromosomal instability.
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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 Socratic graph.