Imperial College London
Portrait Picture

ProfessorChristianSpeck

Faculty of Medicine, Institute of Clinical Sciences

Professor of Genome Biochemistry & Molecular Biology
 
 
 
//

Contact

 

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

 
 
//

Location

 

2.14BLMS BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Sun:2014:10.1101/gad.242313.114,
author = {Sun, J and Fernandez-Cid, A and Riera, A and Tognetti, S and Yuan, Z and Stillman, B and Speck, C and Li, H},
doi = {10.1101/gad.242313.114},
journal = {Genes and Development},
pages = {2291--2303},
title = {Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and function},
url = {http://dx.doi.org/10.1101/gad.242313.114},
volume = {28},
year = {2014}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Eukaryotic cells license each DNA replication origin during G1 phase by assembling a prereplication complex that contains a Mcm2–7 (minichromosome maintenance proteins 2–7) double hexamer. During S phase, each Mcm2–7 hexamer forms the core of a replicative DNA helicase. However, the mechanisms of origin licensing and helicase activation are poorly understood. The helicase loaders ORC–Cdc6 function to recruit a single Cdt1–Mcm2–7 heptamer to replication origins prior to Cdt1 release and ORC–Cdc6–Mcm2–7 complex formation, but how the second Mcm2–7 hexamer is recruited to promote double-hexamer formation is not well understood. Here, structural evidence for intermediates consisting of an ORC–Cdc6–Mcm2–7 complex and an ORC–Cdc6–Mcm2–7–Mcm2–7 complex are reported, which together provide new insights into DNA licensing. Detailed structural analysis of the loaded Mcm2–7 double-hexamer complex demonstrates that the two hexamers are interlocked and misaligned along the DNA axis and lack ATP hydrolysis activity that is essential for DNA helicase activity. Moreover, we show that the head-to-head juxtaposition of the Mcm2–7 double hexamer generates a new protein interaction surface that creates a multisubunit-binding site for an S-phase protein kinase that is known to activate DNA replication. The data suggest how the double hexamer is assembled and how helicase activity is regulated during DNA licensing, with implications for cell cycle control of DNA replication and genome stability.
AU  - Sun,J
AU  - Fernandez-Cid,A
AU  - Riera,A
AU  - Tognetti,S
AU  - Yuan,Z
AU  - Stillman,B
AU  - Speck,C
AU  - Li,H
DO  - 10.1101/gad.242313.114
EP  - 2303
PY  - 2014///
SN  - 0890-9369
SP  - 2291
TI  - Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and function
T2  - Genes and Development
UR  - http://dx.doi.org/10.1101/gad.242313.114
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000343640000008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://genesdev.cshlp.org/content/28/20/2291
UR  - http://hdl.handle.net/10044/1/18509
VL  - 28
ER  -
Download