ArticleGenes & development2011
The effect of the intra-S-phase checkpoint on origins of replication in human cells.
Article in Genes & development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 82 citations in OpenAlex.
- Dynamic regulation of origin firing factors links CDK activity to dormant origin activation.Nature communications · 2026Article
- Topological stress regulates replication fork dynamics in unperturbed S phase.Nature communications · 2026Article
- miR-215-5p Suppresses Proliferation/Cell-Cycle Progression and Promotes Apoptosis via Targeting CTCF in Goat Mammary Epithelial Cells.Animals : an open access journal from MDPI · 2026Article
- Specific origin selection and excess functional MCM2-7 loading in ORC-deficient cells.Nucleic acids research · 2025Article
- The multifaceted roles of the Ctf4 replisome hub in the maintenance of genome integrity.DNA repair · 2024Review
- Article
- The cytosolic iron-sulfur cluster assembly (CIA) pathway is required for replication stress tolerance of cancer cells to Chk1 and ATR inhibitors.NPJ breast cancer · 2021Article
- RNF4 Regulates the BLM Helicase in Recovery From Replication Fork Collapse.Frontiers in genetics · 2021Article
- Genome-wide Nucleotide-Resolution Mapping of DNA Replication Patterns, Single-Strand Breaks, and Lesions by GLOE-Seq.Molecular cell · 2020Article
- Article
- A consensus set of genetic vulnerabilities to ATR inhibition.Open biology · 2019Article
- Differential Sensitivity to CDK2 Inhibition Discriminates the Molecular Mechanisms of CHK1 Inhibitors as Monotherapy or in Combination with the Topoisomerase I Inhibitor SN38.ACS pharmacology & translational science · 2019Article
- On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway.Genes · 2019Review
- Transcription shapes DNA replication initiation and termination in human cells.Nature structural & molecular biology · 2019Article
- Monitoring early S-phase origin firing and replication fork movement by sequencing nascent DNA from synchronized cells.Nature protocols · 2019Article
- ATR-Mediated Global Fork Slowing and Reversal Assist Fork Traverse and Prevent Chromosomal Breakage at DNA Interstrand Cross-Links.Cell reports · 2018Article
- The organization of genome duplication is a critical determinant of the landscape of genome maintenance.Genome research · 2018Article
- Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress.Nature · 2018Article
- CKS Proteins Promote Checkpoint Recovery by Stimulating Phosphorylation of Treslin.Molecular and cellular biology · 2017Article
- The essential kinase ATR: ensuring faithful duplication of a challenging genome.Nature reviews. Molecular cell biology · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Although many chemotherapy drugs activate the intra-S-phase checkpoint pathway to block S-phase progression, not much is known about how and where the intra-S-phase checkpoint regulates origins of replication in human chromosomes. A genomic analysis of replication in human cells in the presence of hydroxyurea (HU) revealed that only the earliest origins fire, but the forks stall within 2 kb and neighboring clusters of dormant origins are activated. The initiation events are located near expressed genes with a preference for transcription start and end sites, and when they are located in intergenic regions they are located near regulatory factor-binding regions (RFBR). The activation of clustered neo-origins by HU suggests that there are many potential replication initiation sites in permissive parts of the genome, most of which are not used in a normal S phase. Consistent with this redundancy, we see multiple sites bound to MCM3 (representative of the helicase) in the region flanking three out of three origins studied in detail. Bypass of the intra-S-phase checkpoint by caffeine activates many new origins in mid- and late-replicating parts of the genome. The intra-S-phase checkpoint suppresses origin firing after the loading of Mcm10, but before the recruitment of Cdc45 and AND-1/CTF4; i.e., after helicase loading but before helicase activation and polymerase loading. Interestingly, Cdc45 recruitment upon checkpoint bypass was accompanied by the restoration of global Cdk2 kinase activity and decrease in both global and origin-bound histone H3 Lys 4 trimethylation (H3K4me3), consistent with the suggestion that both of these factors are important for Cdc45 recruitment.
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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.