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{Yuan:2017:10.1038/nsmb.3372,
author = {Yuan, Z and Riera, A and Bai, L and Sun, J and Nandi, S and Spanos, C and Chen, ZA and Barbon, M and Rappsilber, J and Stillman, B and Speck, C and Li, H},
doi = {10.1038/nsmb.3372},
journal = {Nature Structural & Molecular Biology},
pages = {316--324},
title = {Structural basis of MCM2-7 replicative helicase loading by ORC-Cdc6 and Cdt1},
url = {http://dx.doi.org/10.1038/nsmb.3372},
volume = {24},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - To start DNA replication, the Origin Recognition Complex (ORC) and Cdc6 load a Mcm2-7 double hexamer onto DNA. Without ATP hydrolysis, ORC-Cdc6 recruits one Cdt1-bound Mcm2-7 hexamer, forming an ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) helicase loading intermediate. Here we report a 3.9Å structure of the OCCM on DNA. Flexible Mcm2-7 winged-helix domains (WHD) engage ORC-Cdc6. A three-domain Cdt1 configuration embraces Mcm2, Mcm4, and Mcm6, nearly half of the hexamer. The Cdt1 C-terminal domain extends to the Mcm6 WHD, which binds Orc4 WHD. DNA passes through the ORC-Cdc6 and Mcm2-7 rings. Origin DNA interaction is mediated by an a-helix in Orc4 and positively charged loops in Orc2 and Cdc6. The Mcm2-7 C-tier AAA+ ring is topologically closed by a Mcm5 loop that embraces Mcm2, but the N-tier ring Mcm2-Mcm5 interface remains open. This structure suggests loading mechanics of the first Cdt1-bound Mcm2-7 hexamer by ORC-Cdc6.
AU  - Yuan,Z
AU  - Riera,A
AU  - Bai,L
AU  - Sun,J
AU  - Nandi,S
AU  - Spanos,C
AU  - Chen,ZA
AU  - Barbon,M
AU  - Rappsilber,J
AU  - Stillman,B
AU  - Speck,C
AU  - Li,H
DO  - 10.1038/nsmb.3372
EP  - 324
PY  - 2017///
SN  - 1545-9993
SP  - 316
TI  - Structural basis of MCM2-7 replicative helicase loading by ORC-Cdc6 and Cdt1
T2  - Nature Structural & Molecular Biology
UR  - http://dx.doi.org/10.1038/nsmb.3372
UR  - https://www.nature.com/articles/nsmb.3372
UR  - http://hdl.handle.net/10044/1/43837
VL  - 24
ER  -
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