Academic literature on the topic 'Cell Cycle Proteins Chromosome Segregation'

Cells divide for three main reasons: growth and development, replace worn-out or injured cells, and reproduction of offspring. Cell division is part of the cell cycle divided into five distinct phases. The diploid state of the cell is the normal chromosomal number in species. During sexual reproduction, the cell's chromosome number is reduced to a haploid state to ensure constancy in chromosome number and thus continuation of the species. The process of cell division is controlled by regulatory proteins. Mitosis occurs in all body cells and is divided into four phases. Meiosis, which occurs in only the germ cells involved in reproduction, divides the chromosomes in two rounds termed meiosis I and meiosis II (reduction division). The human lifecycle starts with gametogenesis, the process that forms gametes which then combine to form a zygote. The zygote quickly becomes an embryo and develops rapidly into a foetus. This chapter explores cell division.

Eukaryotic cells use homologous recombination (HR), classical end-joining (C-NHEJ), and alternative end-joining (Alt-EJ) to repair DNA double-strand breaks (DSBs). Repair pathway choice is controlled by the activation and activity of pathways specific proteins in eukaryotes. Activity may be regulated by cell cycle stage, tissue type, and differentiation status. Bioflavonoids and other environmental agents such as pesticides have been shown to biochemically act as inhibitors of topoisomerase II (Top2). In cells, bioflavonoids directly lead to DNA double-strand breaks through both Top2-dependent and independent mechanisms, as well as induce DNA damage response (DDR) signaling, and promote alternative end-joining and chromosome alterations. This chapter will present differences in expression and activity of proteins in major DNA repair pathways, findings of Top2 inhibition by bioflavonoids and cellular response, discuss how these compounds trigger alternative end-joining, and conclude with implications for genome instability and human disease.

Genetics is the study of heredity. Each individual’s makeup, or phenotype, is determined by nature and modified by environmental factors. DNA identity analysis is based strictly on heredity, and only in the rare case where a human had a bone marrow transplant would the white blood cell genotype differ from that inherited. Difficulties can arise with specimens because of DNA degradation or contamination by extraneous materials, and mixed cell populations could be present in tumorous tissue. The analyst must always be cognizant of these complicating factors. The concept of the gene was advanced by the Moravian monk Gregor Mendel in 1865 based on observations he made after crossing different varieties of garden peas; these experiments are considered the beginning of the discipline of genetics. (The term gene was actually coined by the Danish plant scientist W. Johannsen in the early 1900s.) Mendel formulated two laws. The law of segregation or separation states that two members of each gene pair (alleles) in a diploid organism separate to different gametes during sex cell formation. The law of independent assortment states that members of different pairs of alleles, if located on separate chromosomes or far apart on the same homologous chromosome pair, assort independently into gametes. These laws are basic to the understanding of biological family relationships and play a critical role in such contemporary issues as paternity testing and immigration disputes. The basic unit of life is the cell. Cells are microfactories in which raw materials (amino acids, simple carbohydrates, lipids, and trace elements) are received, new substances (proteins, complex lipids, carbohydrates, and nucleic acids) are produced, and wastes are removed. The thousands of different enzymes required for the myriad ongoing chemical reactions are key to the efficient functioning of cells. Each cell has the ability to self-replicate using the deoxyribonucleic acid (DNA) code as the blueprint, raw materials as building blocks, and enzymes as catalysts. It has been estimated that the average human being is composed of approximately 100 trillion cells—a considerable amount of DNA.

The basic structures of a bacterial and a eukaryotic cell are shown in Fig. 8.1. The differences whose origins call for an explanation are as follows: • The bacterial cell has a rigid outer cell wall, usually made of the peptidoglycan, murein. In eukaryotes, the rigid cell wall is not universal, and cell shape is maintained primarily by an internal cytoskeleton of filaments and microtubules. • Eukaryotic cells have a complex system of internal membranes, including the nuclear envelope, endoplasmic reticulum and lysosomes. • Bacteria have a single circular chromosome, attached to the rigid outer cell wall. In eukaryotes, linear chromosomes are contained within a nuclear envelope, which separates transcription from translation: communication between nucleus and cytoplasm is via pores in the nuclear envelope. • Eukaryotes have a complex cytoskeleton. The actomyosin system powers cell division, phagocytosis, amoeboid motion and the overall contractility to resist osmotic swelling. Microtubules and the associated motor proteins (kinesin, dynein and dynamin) ensure the accurate segregation of chromosomes in mitosis, ciliary motility and the movement of transport vesicles. Intermediate filaments form the structural basis for the association of the endomembranes and nuclear-pore complexes with the chromatin to form the nuclear envelope, while other intermediate filaments help to anchor the nucleus in the cytoplasm. One crucial difference between prokaryotes and most eukaryotes has been omitted from Fig. 8.1: this is the presence of mitochondria, and, in plants and algae, of chloroplasts. The reason for the omission is that, on the scenario for eukaryote origins that seems to us most plausible, these intracellular organelles originated later in time than the structures shown in the figure. The differences between these cell types justifies the recognition of two empires of life (above the kingdom level): Bacteria and Eukaryota (Cavalier-Smith, 199la; Table 8.1). (It is interesting that this taxonomic rank was recognized by Linnaeus.) Within each of the empires, there are two major categories: Bacteria consist of the kingdoms Eubacteria and Archaebacteria, and Eukaryota are divided into the superkingdoms Archaezoa and Metakaryota. The justification for these divisions is as follows. The Archaebacteria, in contrast to the Eubacteria, never have murein cell walls, and their single cell membrane contains isoprenoidal ether rather than acyl ester lipids.