Cyclin binding Cy motifs have multiple activities in the initiation of DNA replication

Hossain, Manzar, Bhalla, Kuhulika, Stillman, Bruce (June 2019) Cyclin binding Cy motifs have multiple activities in the initiation of DNA replication. bioRxiv. (Unpublished)

DOI: 10.1101/681668


<h4>Summary</h4> The initiation of DNA replication involves the 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 in ORC1 and CDC6, including Cyclin-binding (Cy) motifs, mediate Cyclin-CDK dependent and independent protein-protein interactions, conditional on cell cycle phase. The ORC1 Cy motif mediates an auto-regulatory self-interaction, and the same Cy motif prevents CDC6 binding to ORC1 in mitosis, but then facilitates the destruction of ORC1 in S phase. In contrast, in G1, the CDC6 Cy motif promotes ORC1-CDC6 interaction independent of Cyclin-CDK protein phosphorylation. CDC6 interaction with ORC also requires a basic region of ORC1 that in yeast mediates ORC-DNA interactions. We also demonstrate that protein phosphatase 1 binds directly to a SLiM in ORC1, causing de-phosphorylation upon mitotic exit. Thus, Cy-motifs have wider roles, functioning as a ligand and as a degron.

Item Type: Paper
CSHL Authors:
Communities: CSHL labs > Stillman lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 24 June 2019
Date Deposited: 11 Feb 2021 18:14
Last Modified: 11 Feb 2021 18:14

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