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Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication.
Hossain, Manzar; Bhalla, Kuhulika; Stillman, Bruce.
Afiliação
  • Hossain M; Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
  • Bhalla K; Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
  • Stillman B; Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. Electronic address: stillman@cshl.edu.
Mol Cell ; 81(9): 1951-1969.e6, 2021 05 06.
Article em En | MEDLINE | ID: mdl-33761311
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Núcleo Celular / Proteínas de Ciclo Celular / Replicação do DNA / Complexo de Reconhecimento de Origem / Proteínas Intrinsicamente Desordenadas / ATPases Associadas a Diversas Atividades Celulares / Mitose Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Núcleo Celular / Proteínas de Ciclo Celular / Replicação do DNA / Complexo de Reconhecimento de Origem / Proteínas Intrinsicamente Desordenadas / ATPases Associadas a Diversas Atividades Celulares / Mitose Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article