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The Origin Recognition Complex: where it all begins
Author(s) -
JoshuaTor Leemor,
Tocilj Ante,
On Kenneth,
Yuan Zuanning,
Sun Jingchuan,
Li Huilin,
Stillman Bruce
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.245.1
Subject(s) - origin recognition complex , origin of replication , dna replication factor cdt1 , dna replication , crystallography , replication (statistics) , biology , computational biology , chemistry , stereochemistry , eukaryotic dna replication , dna , genetics , virology
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. I will present 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. Support or Funding Information Howard Hughes Medical Institute National Institutes of Health This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .