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Denucleation in Erythrocytes: B-DNA, Single-Stranded DNA and Z-DNA

During the last several decades research on cell death has been proliferating at a fast rate. Regulated cell death is important not only in morphogenesis, but also in the removal of damaged or neoplastic cells and the optimization of immunological factors [1]. Three types of cell death can occur among a variety of tissue types: apoptosis , necrosis and terminal differentiation (denucleation). Terminal differentiation may be considered a very specialized form of apoptosis that has evolved to serve tissue-specific function [1]. DNA is no longer considered a static molecule, but rather a dynamic entity [5]. Alternative forms of the more widely present B-DNA can exist in cells, such as Z-DNA [5]. The expulsion of the mammalian nucleus from erythroblasts has been the focus of many studies over the past forty-five years [2,3]. The final product of mammalian erythropoiesis, a very complicated process, is a non-nucleated red blood cell. The mammalian reticulocyte lacks a nucleus and is incapable of further cell division or differentiation to another cell type. It should be noted that many other species produce nucleated red blood cells. The precise mechanism of mammalian erythropoiesis (terminal differentiation) is not yet fully understood, especially on a nucleic acids level: B-DNA, Z-DNA, Z-RNA [6]. Controversy still exists as to whether the loss of nuclei from mammalian erythroblasts occurs by extrusion, by karyolysis or a combination of both mechanisms. The specific purpose of this research project was to examine the molecular biology of the immature red blood cells, and specifically examine the role of denucleation on the different types of nuclear DNA helical structures: right-handed double-stranded (ds-) B-DNA, left-handed ds-Z-DNA and denatured single-stranded (ss-) DNA.