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Cells propagate by making copies of themselves via genome replication. Arguably, replication of DNA is the most fundamental and conserved mechanism of all life forms. Cracking the secret of how this process is achieved with the utmost accuracy is the key to understanding the secret of life. When Watson and Crick first proposed how DNA is replicated based on the structure of the DNA double helix more than a half-century ago, many believed that the structure of the machinery that separates the two strands of DNA for replication would be forthcoming. However, the replication machine turns out to be much more complicated than previously imagined because of its large size, its tripartite nature (it is made up of three engines) and flexibility. Structural information for the DNA replication machinery at atomic resolution by conventional methods was not available until very recently with the advent of the resolution revolution of cryo-EM technology.
A series of articles published by the Tye (HKUST)/Gao (Peking University) collaboration opens the door for deciphering the function of the DNA replication machinery at unprecedented resolutions. The first, published in Nature 2015, determined the structure of the core engine of the DNA replication machine called the MCM complex. The second reported an open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer. The third now appears in Nature, detailing the atomic structure of the Origin Recognition Complex (ORC) that selects start sites genome-wide to initiate DNA replication.
Cell - Egg - Cell - Divisions - Cell
Every human came from a single cell (fertilized egg) after approximately 1016 cell divisions. Each cell division requires the exact replication of the genome such that each daughter cell receives a complete complement of the identical genetic information in the form of DNA. Aberrant DNA replication that results in deregulated cell divisions is the cause of many cancers and...
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