ArticleCell cycle (Georgetown, Tex.)2015
RHINO forms a stoichiometric complex with the 9-1-1 checkpoint clamp and mediates ATR-Chk1 signaling.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- A RHNO1-ATR/Chk1 positive feedback loop sustains the DNA replication stress response.bioRxiv : the preprint server for biology · 2026Article
- Energetically equivalent structural transitions in the Rad17-Rad9-Hus1-Rad1-Rhino complex underlie the sequential progression from activation through maintenance to inactivation of the ATR-dependent DNA damage response.Nucleic acids research · 2026Article
- Defects in DNA damage signaling and cell cycle checkpoints in a mouse model of Rhno1 deletion.Cell death discovery · 2025Article
- FOXM1 expression reverts aging chromatin profiles through repression of the senescence-associated pioneer factor AP-1.Nature communications · 2025Article
- Review
- RHINO directs MMEJ to repair DNA breaks in mitosis.Science (New York, N.Y.) · 2023Article
- Multiple 9-1-1 complexes promote homolog synapsis, DSB repair, and ATR signaling during mammalian meiosis.eLife · 2022Article
- Phosphorylation-dependent assembly of DNA damage response systems and the central roles of TOPBP1.DNA repair · 2021Review
- Structural basis for proficient oxidized ribonucleotide insertion in double strand break repair.Nature communications · 2021Article
- PHF8-promoted TOPBP1 demethylation drives ATR activation and preserves genome stability.Science advances · 2021Article
- Co-regulation and function ofeLife · 2021Article
- Review
- Biochemical analysis of TOPBP1 oligomerization.DNA repair · 2020Article
- ATR signaling in mammalian meiosis: From upstream scaffolds to downstream signaling.Environmental and molecular mutagenesis · 2020Review
- Structure of the RAD9-RAD1-HUS1 checkpoint clamp bound to RHINO sheds light on the other side of the DNA clamp.The Journal of biological chemistry · 2020Article
- Investigation of the Possible Role of RAD9 in Post-Diapaused Embryonic Development of the Brine ShrimpGenes · 2019Article
- Common motifs in ETAA1 and TOPBP1 required for ATR kinase activation.The Journal of biological chemistry · 2019Article
- Quantitative phosphoproteomics reveals mitotic function of the ATR activator ETAA1.The Journal of cell biology · 2019Article
- Article
- Mechanisms for stalled replication fork stabilization: new targets for synthetic lethality strategies in cancer treatments.EMBO reports · 2018Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The ATR-Chk1 signaling pathway mediates cellular responses to DNA damage and replication stress and is composed of a number of core factors that are conserved throughout eukaryotic organisms. However, humans and other higher eukaryotic species possess additional factors that are implicated in the regulation of this signaling network but that have not been extensively studied. Here we show that RHINO (for Rad9, Rad1, Hus1 interacting nuclear orphan) forms complexes with both the 9-1-1 checkpoint clamp and TopBP1 in human cells even in the absence of treatments with DNA damaging agents via direct interactions with the Rad9 and Rad1 subunits of the 9-1-1 checkpoint clamp and with the ATR kinase activator TopBP1. The interaction of RHINO with 9-1-1 was of sufficient affinity to allow for the purification of a stable heterotetrameric RHINO-Rad9-Hus1-Rad1 complex in vitro. In human cells, a portion of RHINO localizes to chromatin in the absence of DNA damage, and this association is enriched following UV irradiation. Furthermore, we find that the tethering of a Lac Repressor (LacR)-RHINO fusion protein to LacO repeats in chromatin of mammalian cells induces Chk1 phosphorylation in a Rad9- and Claspin-dependent manner. Lastly, the loss of RHINO partially abrogates ATR-Chk1 signaling following UV irradiation without impacting the interaction of the 9-1-1 clamp with TopBP1 or the loading of 9-1-1 onto chromatin. We conclude that RHINO is a bona fide regulator of ATR-Chk1 signaling in mammalian cells.
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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.