{"doi":"10.26508/lsa.201800270","title":"Human CST suppresses origin licensing and promotes AND-1/Ctf4 chromatin association","abstract":"<jats:p>Human CTC1-STN1-TEN1 (CST) is an RPA-like single-stranded DNA-binding protein that interacts with DNA polymerase α-primase (pol α) and functions in telomere replication. Previous studies suggest that CST also promotes replication restart after fork stalling. However, the precise role of CST in genome-wide replication remains unclear. In this study, we sought to understand whether CST alters origin licensing and activation. Replication origins are licensed by loading of the minichromosome maintenance 2–7 (MCM) complex in G1 followed by replisome assembly and origin firing in S-phase. We find that CST directly interacts with the MCM complex and disrupts binding of CDT1 to MCM, leading to decreased origin licensing. We also show that CST enhances replisome assembly by promoting AND-1/pol α chromatin association. Moreover, these interactions are not dependent on exogenous replication stress, suggesting that CST acts as a specialized replication factor during normal replication. Overall, our findings implicate CST as a novel regulator of origin licensing and replisome assembly/fork progression through interactions with MCM, AND-1, and pol α.</jats:p>","journal":"Life Science Alliance","year":2019,"id":663368,"datarank":0.5416376868966337,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.0,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"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":1731927,"name":"Kathryn S Brady","orcid":null,"position":1,"is_corresponding":false},{"id":1731928,"name":"Benjamin P Caiello","orcid":null,"position":2,"is_corresponding":false},{"id":1731929,"name":"Stephanie M Ackerson","orcid":null,"position":3,"is_corresponding":false},{"id":404427,"name":"Jason A. Stewart","orcid":"0000-0003-4969-5440","position":4,"is_corresponding":false},{"id":1422091,"name":"Yilin Wang","orcid":"0009-0003-7583-4704","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Human CST suppresses origin licensing and promotes AND-1/Ctf4 chromatin association","abstract":"<jats:p>Human CTC1-STN1-TEN1 (CST) is an RPA-like single-stranded DNA-binding protein that interacts with DNA polymerase α-primase (pol α) and functions in telomere replication. Previous studies suggest that CST also promotes replication restart after fork stalling. However, the precise role of CST in genome-wide replication remains unclear. In this study, we sought to understand whether CST alters origin licensing and activation. Replication origins are licensed by loading of the minichromosome maintenance 2–7 (MCM) complex in G1 followed by replisome assembly and origin firing in S-phase. We find that CST directly interacts with the MCM complex and disrupts binding of CDT1 to MCM, leading to decreased origin licensing. We also show that CST enhances replisome assembly by promoting AND-1/pol α chromatin association. Moreover, these interactions are not dependent on exogenous replication stress, suggesting that CST acts as a specialized replication factor during normal replication. Overall, our findings implicate CST as a novel regulator of origin licensing and replisome assembly/fork progression through interactions with MCM, AND-1, and pol α.</jats:p>","is_dataset_classified":null,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30979824","pmcid":"PMC6464128","openalex_id":"https://openalex.org/W2915071342","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"R00GM104409","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"P20 GM109091","title":null},{"funder_name":"National Institutes of Health","grant_id":"3P20GM109091-08S2","title":"METABOLIC ANALYSIS INSTRUMENTATION TO ENHANCE TARGETED THERAPEUTICS STUDIES"},{"funder_name":"National Institutes of Health","grant_id":"5R00GM104409-03","title":"Roles of the mammalian CST complex in DNA replication and chromosome cohesion"},{"funder_name":"Honors College Senior Thesis/Project Grant","grant_id":"","title":null},{"funder_name":"Magellan Scholar Program","grant_id":"","title":null},{"funder_name":"University of South Carolina","grant_id":"","title":null}],"total_grants":7,"fwci":1.5197,"citation_percentile":0.82525476,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":5},{"year":2021,"count":10},{"year":2022,"count":4},{"year":2023,"count":5},{"year":2024,"count":8},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.life-science-alliance.org/content/lsa/2/2/e201800270.full.pdf","host_type":"journal"},{"url":"https://www.life-science-alliance.org/content/lsa/2/2/e201800270.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.26508/lsa.201800270","host_type":"publisher"},{"url":"https://doi.org/10.26508/lsa.201800270","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30979824","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6464128","host_type":"repository"},{"url":"https://doaj.org/article/235a43d9a60746c586e0f0cc27712950","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6464128","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6464128?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/561977","host_type":""},{"url":"http://dx.doi.org/10.26508/lsa.201800270","host_type":""},{"url":"https://dx.doi.org/10.26508/lsa.201800270","host_type":""},{"url":"https://dx.doi.org/10.1101/561977","host_type":""},{"url":"http://dx.doi.org/10.1101/561977","host_type":""}],"fields_of_study":["DNA Repair Mechanisms","Genomics and Chromatin Dynamics","Telomeres, Telomerase, and Senescence","0301 basic medicine","0303 health sciences","03 medical and health sciences","Cell Cycle Proteins","Chromatin","DNA Polymerase I","DNA Replication","DNA-Binding Proteins","G1 Phase Cell Cycle Checkpoints","Gene Knockdown Techniques","HCT116 Cells","HEK293 Cells","HeLa Cells","Humans","Minichromosome Maintenance Proteins","RNA, Small Interfering","S Phase Cell Cycle Checkpoints","Telomere","Telomere-Binding Proteins"],"mesh_terms":["Chromatin","DNA Polymerase I","DNA Replication","DNA-Binding Proteins","HeLa Cells","Humans","Telomere","Cell Cycle Proteins","Telomere-Binding Proteins","RNA, Small Interfering","HCT116 Cells","Gene Knockdown Techniques","HEK293 Cells","G1 Phase Cell Cycle Checkpoints","S Phase Cell Cycle Checkpoints","Minichromosome Maintenance Proteins","Hela Cells"],"keywords":["Replisome","Minichromosome maintenance","DNA replication factor CDT1","Pre-replication complex","Origin recognition complex","Biology","DNA replication","Cell biology","Eukaryotic DNA replication","Replication factor C","Control of chromosome duplication","Genetics","Chromatin","DNA","Minichromosome Maintenance Proteins","Telomere-Binding Proteins","Cell Cycle Proteins","Telomere","DNA Polymerase I","HCT116 Cells","G1 Phase Cell Cycle Checkpoints","DNA-Binding Proteins","HEK293 Cells","Gene Knockdown Techniques","S Phase Cell Cycle Checkpoints","Humans","RNA, Small Interfering","Research Articles","HeLa Cells"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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