Chapter 6

The cell cycle is ahighly ordered sequence of events that takes place within a cell and eventually results in cellular division. Cells do not divide continuously - long periods of growth and normal function seperate divisions. These periods are called interphase and a cell spends the majority of its time in this phase. INterphase is sometimes referred to as the resting phase, however it is actually a very active phase when the cell is carrying out its normal functions such as making enzymes and proteins whilst preparing for division. During interphase DNA is replicated and checked for errors in the nucleus, portein synthesis occurs in the cytoplasm, mitochondria grow and divide, chloroplasts grow and divide in plant cells and the normal metabolic processes of cells occur. The three stages of interphase are as follows:

• G1: First growth phase, orgamnelles are produced and replicate, cell increases in size.
• S: Synthesis phase, DNA is replictaed in the nucleus.
• G2: Second growth phase, DNA is checked for errors, cell continues to grow and energy stores increase.

The mitotic phase follows and is the period of cell division, first the nucleus divides in mitosis, and then the cytoplasm divides and two cells are produced in cytokinesis.

G0 is the name given to the phase when the cell leaves the cycle temorarily or permanently, this can be due to:

• Differentiation: A cell that becomes specialised to carry out a specific function is no longer available to divide. It will carry out its function indefinitely and will not enter the cell cycle again.
• The DNA of a cell may be damaged, in which case it is no longer viable, a damaged cell can no longer dividemand enters a period of permanent cell arrest (G0), the majority of normal cells can only divide a number of times before they become senescent (don't divide).
• As you age, the number of senescent cells increases in your body as has linked to many age related diseases.

A few types of cells that enter this phase can be stiumlated to go back into the cell cycle and start dividing again, such as lymphocytes in an immune response.

It is vital to ensure that a cell only divided when it has grown to the right size, the replicated DNA is error free/repaired and the chromosomes are in their correct positions during mitosis. This is to ensure that two identical daughter cells are created. Checkpoints are the control mechanisms of the cell cycle. They monitor and verify whether the processes at each stage of the cycle have been accurately completeted befote the cell is allowed to progress into the next phase. Checkpoints occur at various stages of the cell cycle:

• G1 Checkpoint - This checkpoint is at the end of the G1 phase, before entry into S phase. If the cell does not satisfy the requirements of the checkpoint then it will enter the resting state.
• G2 Checkpoin - This checkpoint is at the end of G2 phase, before the start of the mitotic phase. Inorder to pass this checkpoint the DNA must have been replicated without error and if it is passed the cell iniitaites the molecular processes that sognl the beginning of mitosis.
• Spindle asssmebly checkpoint - This checkpoint is at the point in mitosis where all the chromosomes should be attached to spindles and have aligned correctly, mitosis cannot proceed until this checkpoint is passed. 

The passing of the cell-cycle checkpoint is brought about by kinases, which are a class of enzyme that catalyse the reaction of phosphorylation which changes the tertiary structure of checmpoint proteins, activating them at certain points in the cycle. Kinases involved in regulation are activtaed by binding to a variety of checkpoint proteins called cyclins to form a CDK complex, which catalyse the activation of key cell cycle proteins by phosphorylation, this ensures a cell progresses through different phases of its cycle at appropriate times. Different enzymes break down cyclins when they aren't needed, signalling the cell to move into the next phase.

Cancer is a group of many diseased caused by the uncontrolled division of cells, tumours are oftne the result of damage or spontaneous mutation of the genes that encode the proteins that are involved in regulating the cell cycle, including the checkpoint proteins. For example if overexpression of a cyclin gene results from mutation, the abnormally large quantity of cyclins would disrupt the regulation of the cell cycle resulting in uncontrolled divison. CDK complexes can be used as a possible target for inhibitors in treatment of cancers, the activity of CDKs can be reduced and may lead to reduced or halted cell division. 

Mitosis is the term often used to describe the entire process of cellular division but it actually refers to nuclear division. Mitosis ensures that the daughter cells produced are genetically identical to the parent cell for the growth, replacement and repair of tissues in multicellular organisms, Before mitosis can occur all of the DNA in the nucleus must be replicated, each DNA molecule is convereted to two identical chromatids. The two chromatids are joined at a region called the centromere which is to hold them in place.

Prophase: During this phase chromatiin fibres begin to coil and condese to form chromosomes ( that can take up stain and be visible under a microscope), the nucleolus disappears and the nuiclear envelope brekas down. Protein microtubules form spindle shaped structures linking the poles of the cell and the centrioles (cylindrical bundles of proteins that help spindle formation) migrate to oppposite poles of the cell. The spindle fibres attach to the centromeres and start to move the chromosomes to the centre of the cell.

Metaphase: During metaphase the chromosomes are moved by the spindle fibres to from a plane in the centre of the cell called the metaphase plate and are help in position.

Anaphase: The centromeres holding the chromatids together in each chromosome are pulled apart to opposite poles of the cell by the shortening spindle fibres, seperating the chromatids.

Telophase: In this phase the chromatids have reached the poles and are now chromosomes, the two new sets assemble at each pole as the nuclear envelope reforms around them, the chromosomes start to uncoil and the nucleolus is reformed.

This is the name for the actual division of the cell into two seperate ones and begins in telophase. 

In animal cells a cleavage furrow is formed arounf the middle of the cell and the cell surface membrane is pulled inwards by the cytoskeleton until it is close enough  to fuse around the middle forming two cells.

Plant cells have a cell wall so a cleavage furrow cannot be formed, vesicles from the Golgi apparatus begin to assemble in the same place where the metaphase plate was formed, the vesicles fuse with each other amd the cell surface membrane, dividing the cell into two. New sections of cell wall then form along the new sections of membrane (if this happened before they seperated then osmotic lysis would occur).

In sexual reproduction two gametes fuse to form a zygote. Gametes must only contain only half the standard (diploid) number of chromosomes, and are formed by the process of meiosis where the nucleus divides twice to produce four haploid daughter cells - reduction division. 

Each nucleus of an organisms cells contains two copies of each gene, one from each parent, so each nucleus contains matching sets of chromosomes, called homologous chromosomes and is termed diploid. Genes for particular characteristics will be the same length and position on each chromosome. 

Meiosis is divided into two phases; meiosis I and meiosis II. The first division is the reduction when the homologous chromosomes are seperated into two cells and each one will only contain one full set of genes instead of two - haploid. The second division is similar to mitosis and the pairs of chromatids are seperated to more cells. 

Prophase 1: During this phase, chromosomes condense, the nuclear envelope disintergrates, the nucleolus disappears and spindle formation begins (like mitosis). The difference here is that the homologous chromosomes pair up, forming bivalents and as they are brought together the chromatids can entangle - crossing over. 

Metaphase 1: This is the same as metaphase in mitosis except that the homologous chromosomes assemble along the plate rather than induvidual ones. The orientation of each pair is random and independant of any other. The maternal or paternal chromosomes can end up facing either pole, this is called independant assortment and can result in many different combinations of alleles so results in genetic variation.

Anaphase 1: This is different to mitosis as the homologous chromosomes are pulled to oppposite poles and the chromatids remain joined. Sections of DNA on sister chromatids which became entangled break off ans rejoin resulting in the exchange of DNA - chiasmata. When this occurs recombinant DNA is formed which genes being exchanged between chromatids. This will cause genetic variation and makes the chromatids no longer identical.

Telophase 1 : This is the same as in mitosis, chromosomes assemble at each pole and nucleus divides follow by cytokinesis. 

Prophase 2: In this phase the chromosomes, which still consist of two chromatids, condense and become visible again. The nuclear envelope breaks down and spindle formation begins.

Metaphse 2: This differs form metaphase 1 as the induvidual chromosomes assemble on the plate like in mitosis. Due to crossing over the chromatids are no longer identical so there is independant assortment again and more genetic variation.

Anaphase 2: Unlike anaphase 1 this phase results in the chromatids of the induvidual chromosomes being pulled to opposite poles after the division of the centromeres, like in mitosis.

Telophase 2: The chromatids assemble at the poles and uncoil to form chromatin, the nuclear envelope reforms and cytokinesis results in 4 haploid cells being produced.

Erythrocytes: Red blood cells have a flattened biconcave shape which increases their SA:V ratio, which maximises oxygrn uptake. In mammals they don't don't have a nuclei or many organelles for the same reason, they are also flexible so they can squeeze through narrow capillaries. 

Neutrophils: They have a multi lobed nucleus so they can squeeze through small gaps, the granular cytoplasm has many lysosomes that contain lysozymes to attack pathogens.

Sperm cells: They have a flagellum so they can swim and they have many mitochondria to supply the energy to swim, the acrosome contains digestive enzymes that are released to digest the protective layers around the ovum.

Palaside cells: These are present in the mesophyll and contain chloroplasts that absorb light for photosynthesis. These cells are rectangular box shapes which are packed in a close layers. they have thin cell walls to increase the rate of diffusion and a large vacuole to maintain turgor.

Root hair cells: These are extensions that increase the surface area to maximise uptake of water and minerals.

Guard cells:  These allow carbon dioxide to enter the plant, when they lose water they less swollen due to osmotic forces and change shape, closing to prevent further water loss via transpiration.

A tissue is made up of a collection of differentiated cells that have a specialised function, there are 4 main types in animals, nervous, epithelial, muscle, and connectivre tissue.

Squamous epithelium: Thin layer of cells present when rapid diffusion is needed, it forms the lining of the lungs and the capillaries.

Ciliated epithelium: Made of ciliated epithelial cells that have hair like structures that beat to move mucus, such as in the trachea, goblet cells are also present that screte the mucus to trap any unwanted particleswhich prevents them from reaching the lungs.

Cartilage: This is a connective tissue that contains fibres of elastin and collagen compososed of chondryte cells embedded in an extracellular matrix, it prevents the ends of bones rubbing amongst other things.

Muscle: This is a tissue that needs to be able to contract in order to move bones, skeletal muscle fibes contain microfibrils that contain contractile proteins.

There are mant plant tissues, including epidermis (to cover plant surfaces) and vasculat tissue (for transport). For example:

Epidermis: This is a single layer of closely packed tissues covering the surfaces of plants and is usualy covered by a waxy waterproof cuticle to reduce water loss along with stomata that enable gaseous exchange.

Xylem tissue: This is a type of vascular tissue responsible for transport of water and minerals throughout plants, it is composed of vessel elements that are elongated dead cells whihc are strengthened by lignin to provide structural support for plants.

Phloem tissue; This is another type of vascular tissue responsible for transport of organic nutrients from the leaves to the rest of plant cells, it is composed of columns of sieve tube cells seperated by perforated walls called sieve plates. 

An organ is a collection of tissues that are adapted  to perform a particular function in an organism. Large multicellular organisms have organ systems, such as the digestive system that breaks down large insoluble molecules to small soluble ones and retains water and removes unwanted material, the cardiovascular system that moves blood, and the gaseous exchange system which brings air into the body so the oxygen can be extracted for respiration, and carbon dioxide can be expelled. 

All cells in plants and organisms begin as undifferentiated cells and aren't adapted to any particular function and are unspecialised, and have the potential to differentiate into a range of cells, these are called stem cells. Stem cells are able to undergo division again and again and are the source of the new cells necessary for growth, development and tissue repair. The activity of stem cells has to be strictly controlled as if they divide too slow tossues won't be efficiently replaces, but if there is uncontrolled division then they can form tumours.

Stem cell potency:

• Totipotent: These stemm cells can differentiate into any type of cell. A zygote is a bundle of totipotent cells, which eventually will produce the whole organism and can also differentiate into extra embyonic tissue lile the umbilicus.
• Pluripotent: These stem cells can form all tissue types but not whole organisms, they are present in early embryos once a blastocyst has formed.
• Multipotent: These stem cells can only form a range of cells within a type of tissue and are found in specific areas like bone marrow, nut there is growing evidence to suggest they can be artificially triggered to become pluripotent.

Multicellular organisms have evolved fomr unicellular ones because groups of cells with different functions wokring together is more efficient than single cells operating on their own. In multicellular organisms cells ahve to specialise tp take on different roles, for example all the different types of stem cells specialise form multipotent stem cells found in the bone marrow, for example erythrocytes only live for 120 days due to lack of organelles so have to replaced constantly. 

Stem cells in plants are present in meristematic tissue which is wherever growth is occurring such such as in the tips of roots and shoots. Meristems are also located sandwiched between the phloem and xylem tissue in the vascular cambium so it can grow as the plant does. The pluripotent nature of plant stem cells continous throughout the life of the plant as they continue to grow.

Stem cells transplanted into specific areas have the potential to treat certain diseases such as:

• Heart disease:  Muscle tissue in the heart is damaged as a result of a heart attack, but new tissue could be grown to replace it, and has been done so in some cases.
• Type 1 diabetes: Stem cells that create insulin could be placed into patients without them being destroyed due to autoimmunity.
• Birth defects: Scientists have already irreverisbly reveres previously untreatable defects in model organisms like mice.
• Parkinson's: Stem cells can replace the dead dopamine cells in the brain rhat cause shaking and muscle malfunction.

Stem cells are already used in areas such as:

• The treatment of burns: Stem cells can be grown and grafted to the skin of patients.
• Drug trials: New drugs can be tested on culture stem cells before on animals.
• Developmental biology: Can be used to study the change and development of multicellular life and where things can go wrong.

The use of embyonic stem cells has lead to contreversy as there are religous and moral objections to growing embyos to harvest stem cells and many consider it to be killing something that's alive. This holds back progres and restricts research to multipotent cells, so developments are being made towards artificially transforming multipotent stem cells into pluripotent ones.

Gene therapy using stem cells: Children born with SCID are extremely vunerable to all infections and have no immune system. This is usually treated with a bone marrow transplant but that defends on finding a matching donor. More recently new methods have been developed through removing the patient'w own bone marrow and genetically modifying it so they can function normally and then put back into the patient. This treatment was initally successful but lead to some patients suffering from gene damage.

Plant stem cells and medicines: Plant stem cells have a huge potential role to play in medicine as many drugs originate from plants, and plant stem cells can be cultured leading to an unlimited cheap supply of plant-based drugs.