Imperial College London
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ProfessorChristianSpeck

Faculty of Medicine, Institute of Clinical Sciences

Professor of Genome Biochemistry & Molecular Biology
 
 
 
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Contact

 

+44 (0)7961 815 557chris.speck Website CV

 
 
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Location

 

2.14BLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Feng:2021:10.1038/s41467-021-24199-1,
author = {Feng, X and Noguchi, Y and Barbon, M and Stillman, B and Speck, C and Li, H},
doi = {10.1038/s41467-021-24199-1},
journal = {Nature Communications},
title = {The structure of ORC–Cdc6 on an origin DNA reveals the mechanism of ORC activation by the replication initiator Cdc6},
url = {http://dx.doi.org/10.1038/s41467-021-24199-1},
volume = {12},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. The S. cerevisiae ORC binds to specific DNA sequences throughout the cell cycle but becomes active only when it binds to the replication initiator Cdc6. It has been unclear at the molecular level how Cdc6 activates ORC, converting it to an active recruiter of the Mcm2-7 hexamer, the core of the replicative helicase. Here we report the cryo-EM structure at 3.3 Å resolution of the yeast ORC–Cdc6 bound to an 85-bp ARS1 origin DNA. The structure reveals that Cdc6 contributes to origin DNA recognition via its winged helix domain (WHD) and its initiator-specific motif. Cdc6 binding rearranges a short α-helix in the Orc1 AAA+ domain and the Orc2 WHD, leading to the activation of the Cdc6 ATPase and the formation of the three sites for the recruitment of Mcm2-7, none of which are present in ORC alone. The results illuminate the molecular mechanism of a critical biochemical step in the licensing of eukaryotic replication origins.
AU  - Feng,X
AU  - Noguchi,Y
AU  - Barbon,M
AU  - Stillman,B
AU  - Speck,C
AU  - Li,H
DO  - 10.1038/s41467-021-24199-1
PY  - 2021///
SN  - 2041-1723
TI  - The structure of ORC–Cdc6 on an origin DNA reveals the mechanism of ORC activation by the replication initiator Cdc6
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-021-24199-1
UR  - http://hdl.handle.net/10044/1/90320
VL  - 12
ER  -
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