ArticleThe Journal of biological chemistry2016
Conformational Change of Human Checkpoint Kinase 1 (Chk1) Induced by 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 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Paradoxical non-catalytic kinase functions are driven by inhibitor-induced displacement of autoinhibitory domains.Molecular systems biology · 2026Article
- A C-degron regulates Chk1 kinase by allowing stability of inactive Chk1 and by making it short- lived upon activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The DNA replication machinery transmits dual signals to prevent unscheduled licensing and execution of centrosome duplication.Nature communications · 2025Article
- The anticancer effects of Aronia berry extract are mediated by Chk1 and p53 in colorectal cancer.Phytomedicine : international journal of phytotherapy and phytopharmacology · 2024Article
- CHK1 controls zygote pronuclear envelope breakdown by regulating F-actin through interacting with MICAL3.EMBO reports · 2024Article
- DNA damage-induced proteasome phosphorylation controls substrate recognition and facilitates DNA repair.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Case report: A germlineFrontiers in oncology · 2024Article
- MYO10 regulates genome stability and cancer inflammation through mediating mitosis.Cell reports · 2023Article
- Maternal heterozygous mutation in CHEK1 leads to mitotic arrest in human zygotes.Protein & cell · 2022Article
- Probing Interdomain Linkers and Protein Supertertiary Structure In Vitro and in Live Cells with Fluorescent Protein Resonance Energy Transfer.Journal of molecular biology · 2021Article
- Checkpoint Kinase 1 Pharmacological Inhibition Synergizes with DNA-Damaging Agents and Overcomes Platinum Resistance in Basal-Like Breast Cancer.International journal of molecular sciences · 2020Article
- Chk1-mediated phosphorylation of Cdh1 promotes the SCFCell death & disease · 2020Article
- An ATR and CHK1 kinase signaling mechanism that limits origin firing during unperturbed DNA replication.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Exploration of the molecular mechanisms of cervical cancer based on mRNA expression profiles and predicted microRNA interactions.Oncology letters · 2018Article
- A high content, high throughput cellular thermal stability assay for measuring drug-target engagement in living cells.PloS one · 2018Article
- Intramolecular autoinhibition of checkpoint kinase 1 is mediated by conserved basic motifs of the C-terminal kinase-associated 1 domain.The Journal of biological chemistry · 2017Article
- Hydroxyurea Induces Cytokinesis Arrest in Cells Expressing a Mutated Sterol-14α-Demethylase in the Ergosterol Biosynthesis Pathway.Genetics · 2016Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Phosphorylation of Chk1 by ataxia telangiectasia-mutated and Rad3-related (ATR) is critical for checkpoint activation upon DNA damage. However, how phosphorylation activates Chk1 remains unclear. Many studies suggest a conformational change model of Chk1 activation in which phosphorylation shifts Chk1 from a closed inactive conformation to an open active conformation during the DNA damage response. However, no structural study has been reported to support this Chk1 activation model. Here we used FRET and bimolecular fluorescence complementary techniques to show that Chk1 indeed maintains a closed conformation in the absence of DNA damage through an intramolecular interaction between a region (residues 31-87) at the N-terminal kinase domain and the distal C terminus. A highly conserved Leu-449 at the C terminus is important for this intramolecular interaction. We further showed that abolishing the intramolecular interaction by a Leu-449 to Arg mutation or inducing ATR-dependent Chk1 phosphorylation by DNA damage disrupts the closed conformation, leading to an open and activated conformation of Chk1. These data provide significant insight into the mechanisms of Chk1 activation during the DNA damage response.
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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.