07 Cell Cycle & Cell Division [52]

Cellular Reproduction Asexual reproduction

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Cell Reproduction

New cells arise from pre-existing cells.  Every new cell formed must inherit 

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genetic information and cell organelles.

The process of cell reproduction has three major parts.  Replication of the parental cell's DNA.  Separation of the duplicated DNA into two equally sized groups of chromosomes.  Physical division of entire cells, dividing cytoplasm.

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Cell Reproduction

In higher organisms each cell usually contains two similar copies of each chromosome, called HOMOLOGOUS CHROMOSOMES.  One of these copies is a maternal contribution and the other is a paternal contribution.  Together, these are called a homologous pair and each alone is called a HOMOLOGUE (= 2 chromatids). 

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Eukaryotic Cell Reproduction 

Eukaryotic cells reproduce in two different ways: mitosis and meiosis. 

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Both asexual and sexual reproduction requires cell division.

Most human cells are frequently reproduced and replaced during the life of an individual by mitosis.  The sex cells, sperm and ova, are produced by mei osis in special tissues of male testes and female o varies.  5

Eukaryotic Cell Reproduction

Mitosis is the most common form of cell replication.  Mitosis process is a part of a larger cell cycle which includes periods of preparation f or synthesizing copies of cellular components and division. 

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Mitosis, the equational division and Meiosis, the reductional division.

The cycle occurs continuously in most organisms.

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Cell Cycle

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Cell Cycle

The cell cycle is an ordered set of events of cell growth and division into two daughter cells.  These events can be divided in two brief periods:  Interphase—during which the cell grows, accumulating nutrients needed for mitosis and duplicating its DNA—and  Mitotic phase, during which the cell splits itself into two distinct cells, often called "daughter cells". 

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Phases of the cell cycle

The cell cycle consists of 2 distinct phases:  1. Interphase 

1.1 G1  1.2 S  1.3 G2 

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2. Mitosis

2.1 Nuclear division  2.2 Cytokinesis 

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G1 Phase

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Intensive cellular synthesis: 

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cell organelles, RNA’s, srtrucral and functional proteins, substances produced to stimulate or inhibit the next phase. synthesis of various enzymes that are required in S phase, mainly those needed for DNA replication.

Cell growth occurs. Duration of G1 is highly variable, even among different cells of the same species. Nonproliferative cells in multicellular eukaryotes generally enter the quiescent G0 state from G1 and may remain quiescent for long periods of time, possibly indefinitely (as is often the case for neurons). It is called cell cycle arrest. 10

S Phase (DNA Synthesis Phase)

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The ensuing S phase starts when DNA synthesis occurs; when it is complete, all of the chromosomes have been replicated, i.e., each chromosome has two (sister) chromatids. Rates of RNA transcription and protein synthesis are very low during this phase, exception for histone production.

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G2 Phase The cell then enters the G2 phase, which lasts until the cell enters mitosis.  Mitochondria and chloroplasts begin to devide.  Again, significant protein synthesis occurs during this phase, mainly involving the production of microtubules, which are required mitotic spindle fibers.  Inhibition of protein synthesis during G2 phase prevents the cell from undergoing mitosis. 

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M phase

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The relatively brief M phase consists of nuclear division (karyokinesis) and cytoplasmic division (cytokinesis). In plants and algae, cytokinesis is accompanied by the formation of a new cell wall. Karyokinesis : It is the process of nuclear division, which involves separation of chromatids and their redistribution as chromosomes into daughter cells. Cytokinesis : It is the process of division of the cytoplasm to result in the formation of daughter cells.

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Control of Cell Cycle 1. Role of Protein Kinase 2. Checkpoints 3. Kinase Inhibitors 14

1. Role of Maturatio npromoting factor • cyclin(MPF) dependent kinase (cdk) • cyclin

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Mammalian Cell Cycle

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2. Cell Cycle Checkpoints The cell cycle proceeds by a defined sequence of events where late events depend upon completion of early events.  To monitor this dependency, cells are equipped with the checkpoints which are set at various stages of the cell cycle. 

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The checkpoints are surveillance mechanism and quality control of the genome to maintain genomic integrity. 1. DNA damage checkpoint 2. DNA replication checkpoint 3. Spindle checkpoint and Morphogenesis checkpoint

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Cell Cycle Checkpoints (cont)

1. DNA damage checkpoint : When cells have DNA damages that arrests cell cycle, at least 3 checkpoints: G1/S (G1) checkpoint, intra-S phase checkpoint, and G2/M checkpoint. 2. DNA replication checkpoint (Apoptosis checkpoint): that arrests cell cycle at G2/M transition until DNA replication is complete. 3. Spindle checkpoint and Morphogenesis checkpoint.  The spindle checkpoint arrests cell cycle at M phase until all chromosomes are aligned on spindle. This checkpoint is very important for equal distribution of chromosomes.  Morphogenesis checkpoint detects abnormality in cytoskeleton and arrests cell cycle at G2/M transition.

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Cell Cycle Arrests

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3. Proteins Interplay in Cell Cycle

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Growth arrest and apoptosis are induced by genotoxic stress.

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Cell Cycle Inhibitors - Therapy

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M phase of the Cell Cycle

The relatively brief M phase consists of 

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Karyokinesis / nuclear division : Process of separation of chromatids and their redistribution as chromosomes into daughter cells and

Cytokinesis / cytoplasmic division : Process of division of the cytoplasm to result in the formation of daughter cells. 25

Mitosis

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Just prior to karyokinesis, the cell will be in interphase to undergo DNA replication.  The DNA each chromosome exists as a pair of chromatids joined together by a centromere.

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Mitotic Cell Division

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Metaphase Checkpoint / Spindle Checkpoint

The spindle checkpoint is a regulatory network that monitors spindle integrity and the attachment of chromosomes to the spindle.  In the presence of defects, the checkpoint system arrests cells at the metaphase to anaphase transition.  Lack of metaphase checkpoint in tumor cells. 

1. MAD2 gene encodes protein in kinetochore.  2. Monoattachment of spindle fibers. 

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Metaphase Checkpoint

Microtubule inhibitors: cytochalasin D, - colchicine, - vinblastine

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Cytokinesis

It is the division of cytoplasm.  The furrow in the middle of the cell by actin filaments deepens and divides the cell into two daughter cells. 

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Significance of Mitosis 

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Mitosis forms two daughter cells which will have the same chromosome number and same genetic material as the parent cell, no variation would be introduced, and results in genetic stability within the populations of cells derived from parental cells, as in a clone. The number of cells within an organism increases by mitosis and this process is called hyperplasia. It forms the basis for growth. Mitosis is also responsible for repair and regeneration of the injured and lost parts of the body. If mitotic division goes uncontrolled in any part of the body, it results in the formation of malignant cells. These cells continue to divide resulting in the formation of malignant tumours. This condition is called cancer.

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Meiosis germ cell division

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Meiosis

Cell division that occurs only in the reproductive cells.  The daughter cells will carry half the number of chromosomes and half the amount of genetic material compared to the parent cell, known as reductional division.  Decrease in the chromosome number from the diploid (2n) condition to the haploid (n) condition.  In meiosis, nucleus divides twice successively  first meiotic division (or meiosis I) and  second meiotic division (or meiosis II). 

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Stages of Meiosis

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Stages of Meiosis First Meiotic Division  Reductional division : daughter cells will have half the number of chromosomes as tha t of the parent cell. Second Meiotic Division  Separation of two chromatids of each chromosomes.  Meiosis-II also has a karyokinesis and a cytokinesis.

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Interphase : The Preparatory Phase

Cell organells replicate and size of the cell increases.  DNA molecule undergoes replication.  Each chromosome exists as a pair of chromatids joined together by a centromere. 

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Meiosis

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Prophase I

It is the phase of longest duration and involves a series of significant changes in the chromosomes.  These changes are often described in five substages namely  Leptontene (thin),  Zygotene (synapse),  Pachytene (thick),  diplotene (two),  Diakinesis (across). 

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Leptotene:  Chromosomes shorten and become visible as single structures. In some cases they have a beaded appearance showing densely staining material called chromomeres alternating with nonstaining regions.  Zygotene:  Paternal and maternal chromosomes come together and pair up.  This pairing of homologous chromosmes is called synapsis. The paired chromosomes are described as bivalents.  The bivalents shorten and thicken (spiralisation).  40

Pachytene:  Each chromosome splits into two chromatids and thus each pair will have four chromatids two paternal and two maternal, now called tetrads.  The non-sister chromatids of the paternal and maternal chromosomes overlap each other and joined at several regions along their length. These points are called Chia smata.  Each chiasma is the site of an exchange of genetic material between the two chromatids.  It occurs due to breakage and reunion between the two non-sister chromatids, called genetic recombination. 41

Diplotene:  The chromosomes start separating, called as disjunction.  Diakinesis:  Separation of the chromosomes is now complete with paternal and maternal chromosomes having ex changed portions of chromatids.  The chromosomes condense again.  The chiasmata disappear by sliding towards the tips of the chromatids, called terminalisation.    The nuclear membrane and nucleolus disappear. Asters and spindle fibres make their appearance.

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Meiosis I = separation of homologous 2n

chromosomes n n

n n

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Meiosis II = seaparation of chromatids n

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n n

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n n

n n n n

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Significance of Meiosis

It brings about a reduction in the chromosome number from a diploid (2n) condition to a haploid ( n) condition.  Such a reduction becomes necessary for maintaining the chromosome number.   It provides chance for the appearance of new gene combinations as a result of crossing over.  This situation brings about variations.   It is a division necessary for the formation of gametes in animals and spores in plants. 

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Genetic Independent Assortment

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Spermatoge nesis

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Oogenesis

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Meiosis Mitosis

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