{"doi":"10.1091/mbc.e15-03-0165","title":"Phosphorylation of the Scc2 cohesin deposition complex subunit regulates chromosome condensation through cohesin integrity","abstract":"<jats:p> The cohesion of replicated sister chromatids promotes chromosome biorientation, gene regulation, DNA repair, and chromosome condensation. Cohesion is mediated by cohesin, which is deposited on chromosomes by a separate conserved loading complex composed of Scc2 and Scc4 in Saccharomyces cerevisiae. Although it is known to be required, the role of Scc2/Scc4 in cohesin deposition remains enigmatic. Scc2 is a phosphoprotein, although the functions of phosphorylation in deposition are unknown. We identified 11 phosphorylated residues in Scc2 by mass spectrometry. Mutants of SCC2 with substitutions that mimic constitutive phosphorylation retain normal Scc2–Scc4 interactions and chromatin association but exhibit decreased viability, sensitivity to genotoxic agents, and decreased stability of the Mcd1 cohesin subunit in mitotic cells. Cohesin association on chromosome arms, but not pericentromeric regions, is reduced in the phosphomimetic mutants but remains above a key threshold, as cohesion is only modestly perturbed. However, these scc2 phosphomimetic mutants exhibit dramatic chromosome condensation defects that are likely responsible for their high inviability. From these data, we conclude that normal Scc2 function requires modulation of its phosphorylation state and suggest that scc2 phosphomimetic mutants cause an increased incidence of abortive cohesin deposition events that result in compromised cohesin complex integrity and Mcd1 turnover. </jats:p>","journal":"Molecular Biology of the Cell","year":2015,"id":684696,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"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":516081,"name":"Matthew Hoffman","orcid":"0000-0003-2724-784X","position":1,"is_corresponding":false},{"id":1788824,"name":"Monika Dzieciatkowska","orcid":null,"position":2,"is_corresponding":false},{"id":11001,"name":"Kirk C. Hansen","orcid":"0000-0001-5054-838X","position":3,"is_corresponding":false},{"id":1788826,"name":"Paul C. Megee","orcid":null,"position":4,"is_corresponding":false},{"id":1272450,"name":"Julie Woodman","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Phosphorylation of the Scc2 cohesin deposition complex subunit regulates chromosome condensation through cohesin integrity","abstract":"<jats:p> The cohesion of replicated sister chromatids promotes chromosome biorientation, gene regulation, DNA repair, and chromosome condensation. Cohesion is mediated by cohesin, which is deposited on chromosomes by a separate conserved loading complex composed of Scc2 and Scc4 in Saccharomyces cerevisiae. Although it is known to be required, the role of Scc2/Scc4 in cohesin deposition remains enigmatic. Scc2 is a phosphoprotein, although the functions of phosphorylation in deposition are unknown. We identified 11 phosphorylated residues in Scc2 by mass spectrometry. Mutants of SCC2 with substitutions that mimic constitutive phosphorylation retain normal Scc2–Scc4 interactions and chromatin association but exhibit decreased viability, sensitivity to genotoxic agents, and decreased stability of the Mcd1 cohesin subunit in mitotic cells. Cohesin association on chromosome arms, but not pericentromeric regions, is reduced in the phosphomimetic mutants but remains above a key threshold, as cohesion is only modestly perturbed. However, these scc2 phosphomimetic mutants exhibit dramatic chromosome condensation defects that are likely responsible for their high inviability. From these data, we conclude that normal Scc2 function requires modulation of its phosphorylation state and suggest that scc2 phosphomimetic mutants cause an increased incidence of abortive cohesin deposition events that result in compromised cohesin complex integrity and Mcd1 turnover. </jats:p>","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26354421","pmcid":"PMC4626061","openalex_id":"https://openalex.org/W2289519455","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"T-32 GM008730","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM066213","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM008730","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA046934","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM066213-02","title":"Molecular Anal. of Pericentric Sister Chromatid Cohesion"},{"funder_name":"National Institutes of Health","grant_id":"3P30CA046934-20S2","title":"Cancer Center Support Grant"}],"total_grants":6,"fwci":0.276,"citation_percentile":0.60398425,"influential_citations":0,"citation_trend":[{"year":2016,"count":1},{"year":2017,"count":1},{"year":2019,"count":1},{"year":2020,"count":3},{"year":2022,"count":2},{"year":2025,"count":3}],"oa_status":"closed","license":"CC BY NC SA","oa_locations":[{"url":"https://doi.org/10.1091/mbc.e15-03-0165","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26354421","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4626061","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4626061","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4626061?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1091/mbc.E15-03-0165","host_type":""},{"url":"https://dx.doi.org/10.1091/mbc.e15-03-0165","host_type":""}],"fields_of_study":["Genomics and Chromatin Dynamics","DNA Repair Mechanisms","Fungal and yeast genetics research","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Cohesins","Chromatids","Chromatin","Chromosomal Proteins, Non-Histone","Chromosomes","DNA Repair","Phosphorylation","Saccharomyces cerevisiae","Mass Spectrometry","Cell Cycle Proteins","Chromosome Segregation","Saccharomyces cerevisiae Proteins"],"keywords":["Cohesin","Establishment of sister chromatid cohesion","Biology","Premature chromosome condensation","Chromosome segregation","Cell biology","Sister chromatids","Chromatid","Separase","Chromatin","Genetics","Chromosome","DNA","Gene","Saccharomyces cerevisiae Proteins","DNA Repair","Chromosomal Proteins, Non-Histone","Cell Cycle Proteins","Articles","Saccharomyces cerevisiae","Chromatids","Chromosomes","Mass Spectrometry","Phosphorylation","Cohesins"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T14:46:38.048731Z","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":[]}