Chapter Two Cell Division

2.1 INTRODUCTION

Cell division is a process by which single cell called parent cell divides into two or more cells called daughter cells.

Cell division can be categorised into mitosis,meiosis and binary fission. Mitosis (occuring in eukaryotes) is the process in which the daughter cells formed are capable of undergoing further division.

Meiosis is the another kind of cell division found in eukaryotes in which the daughter cell formed is permanently transformed into gamete and cannot divide again until fertilization.

Binary fission is the process of cell division occuring in prokaryotes, the parent cell get divided to form two or more daughter cells. These daughter cells can then undergo further division.

Cell cycle is a vital process by which a single fertilized egg develops into complete organism , as well as the process by which hair, skin, blood cells, and some internal organs are renewed.

2.2 THE CELL CYCLE

The cell cycle can be described in terms of two broad points:

Period during which cell starts preparing itself for division known as interphase. This is followed by nuclear division (karyokinesis) and cytoplasmic division (cytokinesis).

2.2.1 Interphase

Interphase has three subunits: G1, S and G2. S stands for synthesis, during this period synthesis of DNA takes place.

G1 and G2 (gap 1 and gap 2) are characterized by protein and RNA synthesis. There is no DNA synthesis during this period.

G0 is a resting stage. When cells are not actively dividing they enter into a dormant stage called G0.

It may be omitted when the cells are actively dividing.

2.2.2 Karyokinesis (Nuclear Division) Karyokinesis refers to the process by which nuclear material is distributed equally between two daughter cells. It includes mitosis and meiosis. 2.2.2.1 Mitosis The process of mitosis is carried out in following five sequential steps: 1. Prophase: The replicated chromosomes condense and the mitotic spindle begins to assemble outside the nucleus. 2. Prometaphase: The membrane surrounding the nucleus (nuclear envelope) breaks down and allows the mitotic spindle to contact the chromosomes. 3. Metaphase: All the chromosomes are gathered at the center of the mitotic spindle. 4. Anaphase: The chromosomes are split apart and pulled to opposite sides of the cell. 5. Telophase: The nuclear envelope reassembles around the two new sets of separated chromosomes to form two nuclei . 2.2.2.2 Meiosis

Meiosis is the type of cell division by which germ cells (egg and sperm) are produced. It is the reductional division.

Meiosis comprises of two successive nuclear divisions.

2.2.2.2.1 First division of meiosis 1. Prophase 1: Duplicated chromatin condenses. Each chromosome consists of two, closely associated sister chromatids. Crossing-over can occur during the latter part of this stage. It includes the following stages

Protoleptotene Leptotene Zygotene Pachytene Diplotene Diakinesis

2. Metaphase 1: Homologous chromosomes align at the equatorial plate. 3. Anaphase 1: Homologous pairs separate with sister chromatids remaining together. 4. Telophase 1: Two daughter cells are formed with each daughter containing only one chromosome of the homologous pair. 2.2.2.2.2 Second division of meiosis: Gamete formation 1. Prophase 2: DNA does not replicate. 2. Metaphase 2: Chromosomes align at the equatorial plate. 3. Anaphase 2: Centromeres divide and sister chromatids migrate separately to each pole. 4. Telophase 2: Cell division is complete. Four haploid daughter cells are obtained. 2.2.3 Cytokinesis (Cytoplasmic Division)

During this period division of cytoplasm takes place.This is the final task that a cell must complete to finish its reproduction.

Cytokinesis begins in anaphase and continues on through telophase. The first visible sign of cytokinesis is when the cell begins to pucker in, a process called furrowing.

Furrowing tends to take place at right angles to the axis of the spindle (so that each nucleus is placed in a different cell)

The cytoskeleton is reused to build the next spindle for mitosis. Now the two cells will continue the cell cycle and begin their interphase again.

2.3 CELL CYCLE REGULATION

During the last three decades significant progress has been made in our understanding of regulatory control of stepwise progression of cell cycle that involves alternation between chromosome segregation (anaphase seperation of chromosomes) and chromosome duplication (DNA synthesis).

Progression of cell cycle depends on discrete check points. Phosphorylation (by kinases) and dephosphorylation (by phosphatase) are used to control the activity of the regulatory circuit itself, and to control activities of the substrates that execute the decisions of the regulatory circuit.

Activation and inactivation of M phase kinase during M phase are the critical points in the cell cycle. Activation of M phase kinase at G2/M regulates entry into mitosis.

Activation requires modification of p34/cdk. Inactivation is achieved by destruction of cyclin.

Cell cycle control involves successive phosphorylations and dephosphorylations of cdc2. Cdc2 is the means by which all of the signals that control Cdc2-regulatin kinases & phosphatases, are ultimately integrated into a decision on whether to proceed through the cycle.

The animal cell cycle is controlled by many cdk-cyclin complexes. G0/G1 and G1/S transitions involve cdk inhibitors. Protrein degradation is important in mitosis. Activation of anaphase promoting complex (APC) (= E3 ligase) or cyclosome in yeasts & vertebrates during mitosis involving a large complex (8 subunits) for selecting the substrates, including Pds1p, that are degraded in anaphase.

Progression through mitosis requires all kinetochores to be paired with their homologs.

Unpaired kinetochore causes mad proteins associated with CDC20, in turn APC can not be activated.

During development of a multicellular eukaryotic organism some cells are required to die via programmed cell death or apoptosis.

A major pathway that triggers apoptosis in mammalian cells was discovered via the properties of the Fas (receptor). Gene product Phenotype of loss-of function mutant Arrest in S-phase Arrest in G2 with imperfectly replicated DNA Arrest at start required for Failure to enter S-phase Arrest at start Arrest at G2 Premature passage past mitotic entry (G2) checkpoint, hence small size Arrest at mitotic entry(G2) checkpoint Arrest in mitosis

Catalytic subunit of DNA pol DNA ligase Serine/threonine protein kinase Gene regulatory protein transcription of G1 cyclins G1 cyclins Mitotic cyclins Tyrosine protein kinase Tyrosine protein phosphatase Protein of phosphatase first