ArticleNucleic acids research2020
ATAD5 restricts R-loop formation through PCNA unloading and RNA helicase maintenance at the replication fork.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- DDX17 is required for efficient DSB repair at DNA:RNA hybrid deficient loci.Nucleic acids research · 2022Pooled it
- The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications.Acta pharmaceutica Sinica. B · 2026Review
- R-PLA enables enhanced detection of R-loops in mammalian cells using proximity ligation.Cell reports methods · 2026Article
- DDX5 (p68) and UbE2T as emerging superior cancer therapeutic targets: dual molecular glue target degradation by FL118 for conquering difficult-to-treat cancers.Journal of experimental & clinical cancer research : CR · 2026Review
- R-loop processing via REXO4-RNaseH1-mediated endo- and exo-cleavage coupling mode prevents genome instability and antitumor immunity.Science advances · 2026Article
- The PARP1-EXD2 axis orchestrates R-loop resolution to safeguard genome stability.Nature chemical biology · 2026Article
- INO80 regulates promoter-associated R-loops to coordinate transcription and maintain genome stability in embryonic stem cells.Biological research · 2026Article
- Expressional and prognostic value of cytokine receptor-like factor 3 in liver hepatocellular carcinoma patients via integrated bioinformatics analyses and experiments.SAGE open medicine · 2026Article
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
- GPATCH4 functions as a regulator of nucleolar R-loops in hepatocellular carcinoma cells.Nucleic acids research · 2025Article
- Positioning loss of PARP1 activity as the central toxic event in BRCA-deficient cancer.DNA repair · 2024Review
- The human ATAD5 has evolved unique structural elements to function exclusively as a PCNA unloader.Nature structural & molecular biology · 2024Article
- Synergistic action of human RNaseH2 and the RNA helicase-nuclease DDX3X in processing R-loops.Nucleic acids research · 2024Article
- Polyubiquitinated PCNA triggers SLX4-mediated break-induced replication in alternative lengthening of telomeres (ALT) cancer cells.Nucleic acids research · 2024Article
- ATAD5 functions as a regulatory platform for Ub-PCNA deubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity.Genes & development · 2024Review
- Xrp1 governs the stress response program to spliceosome dysfunction.Nucleic acids research · 2024Article
- Unscheduled excessive R-loops in immune response.Functional & integrative genomics · 2024Article
- Therapeutic effects and mechanisms of berberine on enteritis caused byFrontiers in microbiology · 2024Article
- Transcription-Replication Conflicts as a Source of Genome Instability.Annual review of genetics · 2023Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
R-loops are formed when replicative forks collide with the transcriptional machinery and can cause genomic instability. However, it is unclear how R-loops are regulated at transcription-replication conflict (TRC) sites and how replisome proteins are regulated to prevent R-loop formation or mediate R-loop tolerance. Here, we report that ATAD5, a PCNA unloader, plays dual functions to reduce R-loops both under normal and replication stress conditions. ATAD5 interacts with RNA helicases such as DDX1, DDX5, DDX21 and DHX9 and increases the abundance of these helicases at replication forks to facilitate R-loop resolution. Depletion of ATAD5 or ATAD5-interacting RNA helicases consistently increases R-loops during the S phase and reduces the replication rate, both of which are enhanced by replication stress. In addition to R-loop resolution, ATAD5 prevents the generation of new R-loops behind the replication forks by unloading PCNA which, otherwise, accumulates and persists on DNA, causing a collision with the transcription machinery. Depletion of ATAD5 reduces transcription rates due to PCNA accumulation. Consistent with the role of ATAD5 and RNA helicases in maintaining genomic integrity by regulating R-loops, the corresponding genes were mutated or downregulated in several human tumors.
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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.