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Introduction to Molecular Biology
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Although knowledge of the structure of the replication machinery in eukaryotes is still limited due to its complexity, there are many similarities with the simpler prokaryotes DNA replication process. In eukaryotic cells, DNA exists in the nucleus as a very compact and condensed structure. In order to begin the replication process, this structure must be opened up, so the DNA polymerase enzyme can copy the DNA template. The replication process takes place at a specific site called origin of replication, which is rich in AT content. The first step in DNA replication begins with the binding of the origin recognition complex (ORC) to the origin of replication. ORC complex is a hexamer of related proteins that function as a replication initiation factor that promotes the unwinding or denaturation of DNA. Following the binding of the ORC complex, other proteins (Cdc6/Cdc18 and Cdt1) will bind and coordinate the recruitment of the minichromosome maintenance function (MCM) complex to the origin of replication. The MCM complex is a hexamer and is thought to be the major DNA helicase in eukaryotic organisms. Once the binding of MCM occurs, a fully licensed pre-initiation replication complex (pre-RC) now exists. This process occurs during the G1 phase of the cell cycle and therefore, cannot initiate the replication. Replication only occurs during the S phase. Thus, separating the licensing and activation is a mechanism that ensures only one replication per origin in a cell cycle.
The role of ORC4 in enucleation of Murine Erythroleukemia (MEL) cells is similar to that in oocyte polar body extrusion
Published in Systems Biology in Reproductive Medicine, 2020
Hieu Nguyen, Anna Ung, W. Steven Ward
The Origin Replication Complex (ORC), which is composed of six proteins, ORC1-6, is essential for initiating licensing at DNA replication origins and recruit adaptor molecules necessary for various cellular processes (Takeda et al. 2005). Previously, we reported that ORC4 plays a vital role in polar body extrusion (PBE) in addition to DNA licensing (Nguyen et al. 2015). During oogenesis, developing oocytes go through two round of asymmetric meiotic division in which half of the chromosomes are extruded into polar bodies that are much smaller than the remaining oocyte (Kloc et al. 2012; Wang et al. 2017). We found that ORC4 polymerizes to form a cage that surrounds the chromatin that will expelled from the oocyte during both meiotic divisions, and disrupting this cage by the injection of peptides that block the polymerization also prevented PBE (Nguyen et al. 2017). The newly described function of the ORC4 protein surrounding expelled chromatin suggested that ORC4 could play a similar role in other asymmetric cell divisions.