{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["15(1)"],"submitter":["Wu Y"],"funding":["Research Grants Council, University Grants Committee"],"pubmed_abstract":["In eukaryotes, the origin recognition complex (ORC) faciliates the assembly of pre-replicative complex (pre-RC) at origin DNA for replication licensing. Here we show that the N-terminal intrinsically disordered region (IDR) of the yeast Orc2 subunit is crucial for this process. Removing a segment (residues 176-200) from Orc2-IDR or mutating a key isoleucine (194) significantly inhibits replication initiation across the genome. These Orc2-IDR mutants are capable of assembling the ORC-Cdc6-Cdt1-Mcm2-7 intermediate, which exhibits impaired ATP hydrolysis and fails to be convered into the subsequent Mcm2-7-ORC complex and pre-RC. These defects can be partially rescued by the Orc2-IDR peptide. Moreover, the phosphorylation of this Orc2-IDR region by S cyclin-dependent kinase blocks its binding "],"journal":["Nature communications"],"pagination":["8039"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11399261"],"repository":["biostudies-literature"],"pubmed_title":["Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex."],"pmcid":["PMC11399261"],"pubmed_authors":["Lam WH","Zhai Y","Lin Y","Wu Y","Zhang Q"],"additional_accession":[]},"is_claimable":false,"name":"Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex.","description":"In eukaryotes, the origin recognition complex (ORC) faciliates the assembly of pre-replicative complex (pre-RC) at origin DNA for replication licensing. Here we show that the N-terminal intrinsically disordered region (IDR) of the yeast Orc2 subunit is crucial for this process. Removing a segment (residues 176-200) from Orc2-IDR or mutating a key isoleucine (194) significantly inhibits replication initiation across the genome. These Orc2-IDR mutants are capable of assembling the ORC-Cdc6-Cdt1-Mcm2-7 intermediate, which exhibits impaired ATP hydrolysis and fails to be convered into the subsequent Mcm2-7-ORC complex and pre-RC. These defects can be partially rescued by the Orc2-IDR peptide. Moreover, the phosphorylation of this Orc2-IDR region by S cyclin-dependent kinase blocks its binding ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-06-02T06:30:54.736Z","creation":"2025-04-06T16:09:36.858Z"},"accession":"S-EPMC11399261","cross_references":{"pubmed":["39271725"],"doi":["10.1038/s41467-024-52408-0"]}}