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Structure of the active form of human origin recognition complex and its ATPase motor module

Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of the active form of human ORC determined by X-ray crystallography and cryo-electron microscopy. The c...

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Autores principales: Tocilj, Ante, On, Kin Fan, Yuan, Zuanning, Sun, Jingchuan, Elkayam, Elad, Li, Huilin, Stillman, Bruce, Joshua-Tor, Leemor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291709/
https://www.ncbi.nlm.nih.gov/pubmed/28112645
http://dx.doi.org/10.7554/eLife.20818
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author Tocilj, Ante
On, Kin Fan
Yuan, Zuanning
Sun, Jingchuan
Elkayam, Elad
Li, Huilin
Stillman, Bruce
Joshua-Tor, Leemor
author_facet Tocilj, Ante
On, Kin Fan
Yuan, Zuanning
Sun, Jingchuan
Elkayam, Elad
Li, Huilin
Stillman, Bruce
Joshua-Tor, Leemor
author_sort Tocilj, Ante
collection PubMed
description Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of the active form of human ORC determined by X-ray crystallography and cryo-electron microscopy. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes. A second lobe contains the ORC2/3 subunits. The complex is organized as a double-layered shallow corkscrew, with the AAA+ and AAA+-like domains forming one layer, and the winged-helix domains (WHDs) forming a top layer. CDC6 fits easily between ORC1 and ORC2, completing the ring and the DNA-binding channel, forming an additional ATP hydrolysis site. Analysis of the ATPase activity of the complex provides a basis for understanding ORC activity as well as molecular defects observed in Meier-Gorlin Syndrome mutations. DOI: http://dx.doi.org/10.7554/eLife.20818.001
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spelling pubmed-52917092017-02-06 Structure of the active form of human origin recognition complex and its ATPase motor module Tocilj, Ante On, Kin Fan Yuan, Zuanning Sun, Jingchuan Elkayam, Elad Li, Huilin Stillman, Bruce Joshua-Tor, Leemor eLife Biophysics and Structural Biology Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of the active form of human ORC determined by X-ray crystallography and cryo-electron microscopy. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes. A second lobe contains the ORC2/3 subunits. The complex is organized as a double-layered shallow corkscrew, with the AAA+ and AAA+-like domains forming one layer, and the winged-helix domains (WHDs) forming a top layer. CDC6 fits easily between ORC1 and ORC2, completing the ring and the DNA-binding channel, forming an additional ATP hydrolysis site. Analysis of the ATPase activity of the complex provides a basis for understanding ORC activity as well as molecular defects observed in Meier-Gorlin Syndrome mutations. DOI: http://dx.doi.org/10.7554/eLife.20818.001 eLife Sciences Publications, Ltd 2017-01-23 /pmc/articles/PMC5291709/ /pubmed/28112645 http://dx.doi.org/10.7554/eLife.20818 Text en © 2017, Tocilj et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biophysics and Structural Biology
Tocilj, Ante
On, Kin Fan
Yuan, Zuanning
Sun, Jingchuan
Elkayam, Elad
Li, Huilin
Stillman, Bruce
Joshua-Tor, Leemor
Structure of the active form of human origin recognition complex and its ATPase motor module
title Structure of the active form of human origin recognition complex and its ATPase motor module
title_full Structure of the active form of human origin recognition complex and its ATPase motor module
title_fullStr Structure of the active form of human origin recognition complex and its ATPase motor module
title_full_unstemmed Structure of the active form of human origin recognition complex and its ATPase motor module
title_short Structure of the active form of human origin recognition complex and its ATPase motor module
title_sort structure of the active form of human origin recognition complex and its atpase motor module
topic Biophysics and Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291709/
https://www.ncbi.nlm.nih.gov/pubmed/28112645
http://dx.doi.org/10.7554/eLife.20818
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