ArticleOncogene2006
ERK activity facilitates activation of the S-phase DNA damage checkpoint by modulating ATR function.
Article in Oncogene, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 61 citations in OpenAlex.
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- Variable thresholds for phosphorylation targets of the ERK signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Tenascin C as a novel zinc finger protein 750 target regulating the immunogenicity via DNA damage in lung squamous cell carcinoma.BMC cancer · 2024Article
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- Chemical screening identifies the anticancer properties ofJournal of Cancer · 2023Article
- Case report: Radiographic complete response of radiation-induced glioblastoma to front-line radiotherapy: A report and molecular characterization of two unique cases.Frontiers in neurology · 2023Article
- Testis-specific hnRNP is expressed in colorectal cancer cells and accelerates cell growth mediating ZDHHC11 mRNA stabilization.Cancer medicine · 2022Article
- Suppression of isoprenylcysteine carboxylmethyltransferase compromises DNA damage repair.Life science alliance · 2021Article
- The DNA damage inducible lncRNA SCAT7 regulates genomic integrity and topoisomerase 1 turnover in lung adenocarcinoma.NAR cancer · 2021Article
- Taxol-Resistant Gene 1 (Txr1) Mediates Oxaliplatin Resistance by Inducing Autophagy in Human Nasopharyngeal Carcinoma Cells.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Etoposide-induced DNA damage affects multiple cellular pathways in addition to DNA damage response.Oncotarget · 2018Article
- A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway.Cell death & disease · 2018Article
- BMI1 reduces ATR activation and signalling caused by hydroxyurea.Oncotarget · 2017Article
- ATR-mediated regulation of nuclear and cellular plasticity.DNA repair · 2016Review
- High concentrations of NaCl induce cell swelling leading to senescence in human cells.Molecular and cellular biochemistry · 2016Article
- Nesprin-2-dependent ERK1/2 compartmentalisation regulates the DNA damage response in vascular smooth muscle cell ageing.Cell death and differentiation · 2015Article
- Article
- Rational Combinations of Targeted Agents in AML.Journal of clinical medicine · 2015Review
- Interplay of DNA damage and cell cycle signaling at the level of human replication protein A.DNA repair · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although Erk kinase has been recently reported to function in the DNA damage response, the mechanism governing this process is unknown. We report here that hydroxyurea (HU) activates Erk via MEK1, a process that is sensitized by a constitutively active MEK1 (MEK1Q56P) and attenuated by a dominant-negative MEK1 (MEK1K97M). While ectopic MEK1Q56P sensitized HU-induced S-phase arrest, inhibition of Erk activation via U0126, PD98059, and MEK1K97M attenuated the arrest, and thereby enhanced cells to HU-induced toxicity. Taken together, we demonstrate an important contribution of Erk to the activation of the S-phase DNA damage checkpoint. This can be attributed to Erk's regulatory role in modulating ATR function. Inhibition of Erk activation with U0126/PD98059 and MEK1K97M substantially reduced HU-induced ATR nuclear foci, leading to a dramatic reduction of gammaH2AX and its nuclear foci. Reduction of MEK1 function by a small interference RNA (siRNA) MEK1 and ectopic MEK1K97M significantly decreased HU-induced gammaH2AX. Conversely, ectopic MEK1Q56P enhanced gammaH2AX foci. Furthermore, immunofluorescent and cell fractioning experiments revealed cytosolic and nuclear localization of ATR. HU treatment caused the redistribution of ATR from the cytosol to the nucleus, a process that is inhibited by U0126. Collectively, we show that Erk kinase modulates HU-initiated DNA damage response by regulating ATR function.
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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.