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Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex
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Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex
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Journal Article
Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex
2024
Overview
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 to Mcm2-7 complex, causing a defective pre-RC assembly. Our findings provide important insights into the multifaceted roles of ORC in supporting origin licensing during the G1 phase and its regulation to restrict origin firing within the S phase.
In eukaryotes, the origin recognition complex (ORC) is essential for replication licensing. Here, the authors report that a short motif within the intrinsically disordered region of the yeast Orc2 subunit plays an important role in regulating the licensing process.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 82/83
/ Assembly
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ G1 Phase
/ Humanities and Social Sciences
/ Intrinsically Disordered Proteins - chemistry
/ Intrinsically Disordered Proteins - genetics
/ Intrinsically Disordered Proteins - metabolism
/ Kinases
/ Licenses
/ Mutation
/ Origin Recognition Complex - genetics
/ Origin Recognition Complex - metabolism
/ Replication Origin - genetics
/ S phase
/ Saccharomyces cerevisiae - genetics
/ Saccharomyces cerevisiae - metabolism
/ Saccharomyces cerevisiae Proteins - chemistry
/ Saccharomyces cerevisiae Proteins - genetics
/ Saccharomyces cerevisiae Proteins - metabolism
/ Science
/ Yeast
