ArticleThe Journal of biological chemistry2016
Direct Binding to Replication Protein A (RPA)-coated Single-stranded DNA Allows Recruitment of the ATR Activator TopBP1 to Sites of DNA Damage.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Development of a structurally distinct TopBP1 inhibitor that enhances PARP blockade and reverses osimertinib resistance.Science advances · 2026Article
- Dpb11 facilitates the colocalization of Mec1-Ddc2 with its activators on gapped DNA.Cell reports · 2026Article
- RPA-independent activation of the ATR/CHK1 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Shining light on drug discovery: optogenetic screening for TopBP1 biomolecular condensate inhibitors.NAR cancer · 2025Article
- Molecular interplay between the DNA damage checkpoint kinase Mec1-Ddc2 and its activator Dpb11 on gapped DNA.bioRxiv : the preprint server for biology · 2025Article
- TopBP1 biomolecular condensates as a new therapeutic target in advanced-stage colorectal cancer.eLife · 2025Article
- Chromatin assembly by the histone chaperone HIRA facilitates Human Papillomavirus replication.bioRxiv : the preprint server for biology · 2025Article
- Distinct regulation of ATM signaling by DNA single-strand breaks and APE1.Nature communications · 2024Article
- A small-molecule inhibitor of TopBP1 exerts anti-MYC activity and synergy with PARP inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Review
- Mind the replication gap.Royal Society open science · 2021Review
- MYB117 is a negative regulator of flowering time inPlant signaling & behavior · 2021Article
- Structure-function analysis of TOPBP1's role in ATR signaling using the DSB-mediated ATR activation in Xenopus egg extracts (DMAX) system.Scientific reports · 2021Article
- APE2 Is a General Regulator of the ATR-Chk1 DNA Damage Response Pathway to Maintain Genome Integrity in Pancreatic Cancer Cells.Frontiers in cell and developmental biology · 2021Article
- Human CTC1 promotes TopBP1 stability and CHK1 phosphorylation in response to telomere dysfunction and global replication stress.Cell cycle (Georgetown, Tex.) · 2020Article
- Biochemical analysis of TOPBP1 oligomerization.DNA repair · 2020Article
- A distinct role for recombination repair factors in an early cellular response to transcription-replication conflicts.Nucleic acids research · 2020Article
- Ddc2ATRIP promotes Mec1ATR activation at RPA-ssDNA tracts.PLoS genetics · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
A critical event for the ability of cells to tolerate DNA damage and replication stress is activation of the ATR kinase. ATR activation is dependent on the BRCT (BRCA1 C terminus) repeat-containing protein TopBP1. Previous work has shown that recruitment of TopBP1 to sites of DNA damage and stalled replication forks is necessary for downstream events in ATR activation; however, the mechanism for this recruitment was not known. Here, we use protein binding assays and functional studies in Xenopus egg extracts to show that TopBP1 makes a direct interaction, via its BRCT2 domain, with RPA-coated single-stranded DNA. We identify a point mutant that abrogates this interaction and show that this mutant fails to accumulate at sites of DNA damage and that the mutant cannot activate ATR. These data thus supply a mechanism for how the critical ATR activator, TopBP1, senses DNA damage and stalled replication forks to initiate assembly of checkpoint signaling complexes.
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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.