{"doi":"10.1074/jbc.m114.621532","title":"Phosphorylation of Minichromosome Maintenance 3 (MCM3) by Checkpoint Kinase 1 (Chk1) Negatively Regulates DNA Replication and Checkpoint Activation","abstract":null,"journal":"Journal of Biological Chemistry","year":2015,"id":621686,"datarank":0.5375278407684165,"base_score":3.58351893845611,"endowment":3.58351893845611,"self_citation_contribution":0.5375278407684165,"citation_network_contribution":0.0,"self_endowment_contribution":0.5375278407684165,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":849321,"name":"Franklin Mayca Pozo","orcid":"0000-0003-0926-3336","position":1,"is_corresponding":false},{"id":800495,"name":"Jacob N. Wisotsky","orcid":null,"position":2,"is_corresponding":false},{"id":293631,"name":"Benlian Wang","orcid":null,"position":3,"is_corresponding":false},{"id":1065697,"name":"James W. Jacobberger","orcid":"0000-0002-3092-5157","position":4,"is_corresponding":false},{"id":291509,"name":"Youwei Zhang","orcid":"0000-0001-7953-5929","position":5,"is_corresponding":false},{"id":657631,"name":"Xiangzi Han","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Phosphorylation of Minichromosome Maintenance 3 (MCM3) by Checkpoint Kinase 1 (Chk1) Negatively Regulates DNA Replication and Checkpoint Activation","abstract":"Mechanisms controlling DNA replication and replication checkpoint are critical for the maintenance of genome stability and the prevention or treatment of human cancers. Checkpoint kinase 1 (Chk1) is a key effector protein kinase that regulates the DNA damage response and replication checkpoint. The heterohexameric minichromosome maintenance (MCM) complex is the core component of mammalian DNA helicase and has been implicated in replication checkpoint activation. Here we report that Chk1 phosphorylates the MCM3 subunit of the MCM complex at Ser-205 under normal growth conditions. Mutating the Ser-205 of MCM3 to Ala increased the length of DNA replication track and shortened the S phase duration, indicating that Ser-205 phosphorylation negatively controls normal DNA replication. Upon replicative stress treatment, the inhibitory phosphorylation of MCM3 at Ser-205 was reduced, and this reduction was accompanied with the generation of single strand DNA, the key platform for ataxia telangiectasia mutated and Rad3-related (ATR) activation. As a result, the replication checkpoint is activated. Together, these data provide significant insights into the regulation of both normal DNA replication and replication checkpoint activation through the novel phosphorylation of MCM3 by Chk1. Background: Chk1 and the MCM complex play important roles in DNA replication and replication checkpoint. Results: Chk1 phosphorylates MCM3. Conclusion: Phosphorylation of MCM3 by Chk1 regulates normal DNA replication and checkpoint. Significance: These results provide insights into our understanding of DNA replication control and replication checkpoint activation.","is_dataset_classified":null,"base_score":3.58351893845611,"endowment":3.58351893845611,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25809478","pmcid":"PMC4424366","openalex_id":"https://openalex.org/W2266724717","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"R00 CA126173","title":null},{"funder_name":"National Institutes of Health","grant_id":"R01 CA163214","title":null}],"total_grants":2,"fwci":2.2053,"citation_percentile":0.88314845,"influential_citations":0,"citation_trend":[{"year":2015,"count":1},{"year":2016,"count":4},{"year":2017,"count":8},{"year":2018,"count":3},{"year":2019,"count":4},{"year":2020,"count":3},{"year":2021,"count":1},{"year":2022,"count":2},{"year":2023,"count":1},{"year":2024,"count":5},{"year":2025,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925820485394/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S0021925820485394/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820485394?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820485394?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M114.621532","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.m114.621532","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25809478","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4424366","host_type":"repository"}],"fields_of_study":["DNA Repair Mechanisms","Carcinogens and Genotoxicity Assessment","CRISPR and Genetic Engineering","Alanine","Ataxia Telangiectasia Mutated Proteins","Cell Cycle","Cell Cycle Checkpoints","Cell Line, Tumor","Checkpoint Kinase 1","Chromatin","DNA Damage","DNA Replication","DNA, Single-Stranded","Gene Expression Regulation","HEK293 Cells","HeLa Cells","Humans","Mass Spectrometry","Minichromosome Maintenance Complex Component 3","Phosphorylation","Protein Kinases","Serine","Signal Transduction"],"mesh_terms":["Checkpoint Kinase 1","Alanine","Cell Cycle","Chromatin","DNA Damage","DNA Replication","DNA, Single-Stranded","Gene Expression Regulation","HeLa Cells","Humans","Phosphorylation","Protein Kinases","Serine","Mass Spectrometry","Signal Transduction","Cell Line, Tumor","HEK293 Cells","Cell Cycle Checkpoints","Ataxia Telangiectasia Mutated Proteins","Minichromosome Maintenance Complex Component 3","Hela Cells"],"keywords":["G2-M DNA damage checkpoint","Origin recognition complex","Minichromosome maintenance","CHEK1","Control of chromosome duplication","Eukaryotic DNA replication","Replication factor C","DNA replication factor CDT1","Biology","DNA replication","Cell biology","Checkpoint Kinase 2","Licensing factor","Pre-replication complex","S phase","DNA re-replication","Cell cycle checkpoint","Cancer research","Molecular biology","Phosphorylation","Cell cycle","Protein kinase A","DNA","Genetics","Protein-Serine-Threonine Kinases","Cancer","DNA damage","Signal transduction"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"refseq"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T15:36:11.885963Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}