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Helicase loading: how to build a MCM2-7 double-hexamer.
Riera A, Tognetti S, Speck C. Riera A, et al. Semin Cell Dev Biol. 2014 Jun;30:104-9. doi: 10.1016/j.semcdb.2014.03.008. Epub 2014 Mar 14. Semin Cell Dev Biol. 2014. PMID: 24637008 Review.
A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication.
Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C. Evrin C, et al. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20240-5. doi: 10.1073/pnas.0911500106. Epub 2009 Nov 12. Proc Natl Acad Sci U S A. 2009. PMID: 19910535 Free PMC article.
In the absence of ATPase activity, pre-RC formation is blocked prior to MCM2-7 hexamer dimerization.
Evrin C, Fernández-Cid A, Zech J, Herrera MC, Riera A, Clarke P, Brill S, Lurz R, Speck C. Evrin C, et al. Nucleic Acids Res. 2013 Mar 1;41(5):3162-72. doi: 10.1093/nar/gkt043. Epub 2013 Feb 1. Nucleic Acids Res. 2013. PMID: 23376927 Free PMC article.
An ORC/Cdc6/MCM2-7 complex is formed in a multistep reaction to serve as a platform for MCM double-hexamer assembly.
Fernández-Cid A, Riera A, Tognetti S, Herrera MC, Samel S, Evrin C, Winkler C, Gardenal E, Uhle S, Speck C. Fernández-Cid A, et al. Mol Cell. 2013 May 23;50(4):577-88. doi: 10.1016/j.molcel.2013.03.026. Epub 2013 Apr 18. Mol Cell. 2013. PMID: 23603117
Here we show that MCM2-7 recruitment by ORC/Cdc6 is blocked by an autoinhibitory domain in the C terminus of Mcm6. Interestingly, Cdt1 can overcome this inhibitory activity, and consequently the Cdt1-MCM2-7 complex activates ORC/Cdc6 ATP-hydrolysis to promote helicase load …
Here we show that MCM2-7 recruitment by ORC/Cdc6 is blocked by an autoinhibitory domain in the C terminus of Mcm6. Interestingly, Cdt …
The ORC/Cdc6/MCM2–7 complex, a new power player for regulated helicase loading.
Riera A, Fernández-Cid A, Speck C. Riera A, et al. Cell Cycle. 2013 Jul 15;12(14):2155-6. doi: 10.4161/cc.25336. Cell Cycle. 2013. PMID: 23803736 Free PMC article. No abstract available.
Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA.
Sun J, Evrin C, Samel SA, Fernández-Cid A, Riera A, Kawakami H, Stillman B, Speck C, Li H. Sun J, et al. Nat Struct Mol Biol. 2013 Aug;20(8):944-51. doi: 10.1038/nsmb.2629. Epub 2013 Jul 14. Nat Struct Mol Biol. 2013. PMID: 23851460 Free PMC article.
Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. ...The resulting ORC-Cdc6 helicase loader …
Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-te …
Seeing is believing: the MCM2-7 helicase trapped in complex with its DNA loader.
Riera A, Li H, Speck C. Riera A, et al. Cell Cycle. 2013 Sep 15;12(18):2917-8. doi: 10.4161/cc.26132. Epub 2013 Aug 21. Cell Cycle. 2013. PMID: 23974098 Free PMC article. No abstract available.
The ORC/Cdc6/MCM2-7 complex facilitates MCM2-7 dimerization during prereplicative complex formation.
Evrin C, Fernández-Cid A, Riera A, Zech J, Clarke P, Herrera MC, Tognetti S, Lurz R, Speck C. Evrin C, et al. Nucleic Acids Res. 2014 Feb;42(4):2257-69. doi: 10.1093/nar/gkt1148. Epub 2013 Nov 14. Nucleic Acids Res. 2014. PMID: 24234446 Free PMC article.
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