Endoreplication: the advantage to initiating DNA replication without the ORC?
The endocycle is a developmentally specialized cell cycle that lacks M phase and consists of only S and G phases. Endoreplicating cells acquire high ploidies by multiple rounds of replication without cell divisions in order to increase protein synthesis to support growth and development of the organism. Endoreplication occurs in developmentally specialized cell types after they terminally differentiate. These cells include: ovarian nurse cells and follicle cells, most of the larval tissues in flies and the placenta giant trophoblasts and megakaryocytes in mammals. To date, studies of endoreplication have mainly focused on two aspects: Cyclin-dependent kinase (CDK)-mediated controls to license and re-license replication origins in the absence of mitosis, and development or differentiation signaling pathways that mediate the transition from mitotic replication to endoreplication. The replication initiation machinery itself has not been much studied, partly because it has been generally considered to consist of the same set of factors used in mitotic cycle. Recently we reported a loss-of-function analysis of the Drosophila orc1 gene, which revealed that the Origin Recognition Complex (ORC) is dispensable for endoreplication. This finding is surprising and rather provocative as it runs against the accepted dogma and is expected to stimulate discussion and interest in the identification of the molecular mechanisms of the initiation of endoreplication. What follows is a highly speculative view of how endoreplication occurs in the absence of the ORC and what advantage ORC-independent replication brings to the organism.
The Ohio State Comprehensive Cancer Center, Department of Molecular Cellular and Biochemistry, College of Medicine, Department of Molecular Genetics, College of Biological Science, Ohio State University, Columbus, OH, USA. maki.asano@osumc.edu
Maki
M
Asano
D000818:Animals; D004261:DNA Replication / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics*; D008957:Models, Genetic; D051738:Origin Recognition Complex / Q000235:genetics* / Q000378:metabolism*
D051738:Origin Recognition Complex