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Article: DDK promotes DNA replication initiation: Mechanistic and structural insights
Title | DDK promotes DNA replication initiation: Mechanistic and structural insights |
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Authors | |
Issue Date | 2022 |
Publisher | ELSEVIER. The Journal's web site is located at http://www.elsevier.com/locate/sbi |
Citation | Current Opinion in Structural Biology, How to Cite? |
Abstract | DNA replication initiation in eukaryotes is tightly regulated through two cell-cycle specific processes, replication licensing to install inactive minichromosome maintenance (MCM) double-hexamers (DH) on origins in early G1 phase and origin firing to assemble and activate Cdc45-Mcm2-7-GINS (CMG) helicases upon S phase entry. Two kinases, cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK), are responsible for driving the association of replication factors with the MCM-DH to form CMG helicases for origin melting and DNA unwinding and eventually replisomes for bi- directional DNA synthesis. In recent years, cryo-electron microscopy studies have generated a collection of structural snapshots for the stepwise assembly and remodeling of the replication initiation machineries, creating a framework for understanding the regulation of this fundamental process at a molecular level. Very recent progress is the structural characterization of the elusive MCM-DH-DDK complex, which provides insights into mechanisms of kinase activation, substrate recognition and selection, as well as molecular role of DDK-mediated MCM-DH phosphorylation in helicase activation. |
Persistent Identifier | http://hdl.handle.net/10722/323389 |
DC Field | Value | Language |
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dc.contributor.author | Li, N. | - |
dc.contributor.author | Gao, N. | - |
dc.contributor.author | Zhai, Y | - |
dc.date.accessioned | 2022-12-16T10:04:36Z | - |
dc.date.available | 2022-12-16T10:04:36Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | Current Opinion in Structural Biology, | - |
dc.identifier.uri | http://hdl.handle.net/10722/323389 | - |
dc.description.abstract | DNA replication initiation in eukaryotes is tightly regulated through two cell-cycle specific processes, replication licensing to install inactive minichromosome maintenance (MCM) double-hexamers (DH) on origins in early G1 phase and origin firing to assemble and activate Cdc45-Mcm2-7-GINS (CMG) helicases upon S phase entry. Two kinases, cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK), are responsible for driving the association of replication factors with the MCM-DH to form CMG helicases for origin melting and DNA unwinding and eventually replisomes for bi- directional DNA synthesis. In recent years, cryo-electron microscopy studies have generated a collection of structural snapshots for the stepwise assembly and remodeling of the replication initiation machineries, creating a framework for understanding the regulation of this fundamental process at a molecular level. Very recent progress is the structural characterization of the elusive MCM-DH-DDK complex, which provides insights into mechanisms of kinase activation, substrate recognition and selection, as well as molecular role of DDK-mediated MCM-DH phosphorylation in helicase activation. | - |
dc.language | eng | - |
dc.publisher | ELSEVIER. The Journal's web site is located at http://www.elsevier.com/locate/sbi | - |
dc.relation.ispartof | Current Opinion in Structural Biology | - |
dc.title | DDK promotes DNA replication initiation: Mechanistic and structural insights | - |
dc.type | Article | - |
dc.identifier.email | Zhai, Y: zhai@hku.hk | - |
dc.identifier.authority | Zhai, Y=rp02398 | - |
dc.identifier.hkuros | 343026 | - |