Hossain, Manzar, Bhalla, Kuhulika, Stillman, Bruce
(March 2021)
Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication.
Molecular Cell.
ISSN 1097-2765
Abstract
The initiation of DNA replication involves cell cycle-dependent assembly and disassembly of protein complexes, including the origin recognition complex (ORC) and CDC6 AAA+ ATPases. We report that multiple short linear protein motifs (SLiMs) within intrinsically disordered regions (IDRs) in ORC1 and CDC6 mediate cyclin-CDK-dependent and independent protein-protein interactions, conditional on the cell cycle phase. A domain within the ORC1 IDR is required for interaction between the ORC1 and CDC6 AAA+ domains in G1, whereas the same domain prevents CDC6-ORC1 interaction during mitosis. Then, during late G1, this domain facilitates ORC1 destruction by a SKP2-cyclin A-CDK2-dependent mechanism. During G1, the CDC6 Cy motif cooperates with cyclin E-CDK2 to promote ORC1-CDC6 interactions. The CDC6 IDR regulates self-interaction by ORC1, thereby controlling ORC1 protein levels. Protein phosphatase 1 binds directly to a SLiM in the ORC1 IDR, causing ORC1 de-phosphorylation upon mitotic exit, increasing ORC1 protein, and promoting pre-RC assembly.
| Item Type: |
Paper
|
| Subjects: |
bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Cyclins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > ATPase
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
organs, tissues, organelles, cell types and functions > cell types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
organs, tissues, organelles, cell types and functions > organelles, types and functions > mitosis
organs, tissues, organelles, cell types and functions > organelles, types and functions
organs, tissues, organelles, cell types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > origin recognition complex
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein phosphatase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types |
| CSHL Authors: |
|
| Communities: |
CSHL labs > Stillman lab
CSHL Cancer Center Program
CSHL Cancer Center Program > Gene Regulation and Inheritance Program
CSHL Cancer Center Shared Resources > Antibody and Phage Display Service
CSHL Cancer Center Shared Resources > Microscopy Service |
| SWORD Depositor: |
CSHL Elements
|
| Highlight: |
Stillman, Bruce W. |
| Depositing User: |
CSHL Elements
|
| Date: |
13 March 2021 |
| Date Deposited: |
05 May 2021 18:54 |
| Last Modified: |
13 Feb 2024 17:01 |
| PMCID: |
PMC8106667 |
| URI: |
https://repository.cshl.edu/id/eprint/39990 |
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