Week 2 Lesson 1-cell cycle and mitosis PDF

Title Week 2 Lesson 1-cell cycle and mitosis
Course Genetics and cell biology
Institution Royal Holloway, University of London
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Week 2 : Genetics lesson 1 the cell cycle and mitosis

Lesson 1: Cell cycle and Mitosis -

11.1 all cells derive from other cells 11.2 The eukaryotic cell division cycle is regulated 11.3 Eukaryotic cells divide by mitosis

The first human cells to be grown in a laboratory came from a woman called Henrita Lacks. The cells that came from her were cervical cancer cells, thus grew so well and were later called Hela cells because they reproduced very well. Ordinary human cells don’t want to be in isolation from other cells. Due to signalling from other cells. Hela cells are cancerous and thus they multiply very quickly compared to other cells. Hela cells are cancerous due to the human papilloma virus 18 (HPV 18)

The life cycle of an organism depends on its cell division.   

Cell division is important for growth, repair and asexual reproduction. Regeneration partially in singled cell is due to cell division. Cell division and an increase in cell size is vital for the growth in multicellular organisms.

What are the events of the cell cycle in prokaryotes and eukaryotes?    

A reproductive signal Replication of DNA Segregation: distribution of DNA into two new cells -daughter cells Cytokinesis; separation of cellular material into two new cells-includes the mitochondria which is present in the cytoplasm of the cell.

Explain the process of Binary fission in prokaryotic cells   



Bacteria are a type of prokaryotes; thus, they have no membrane bound organelles, no distinct nucleus. Their division is thus through binary fission It has a reproductive signal such as food which initiates the cell division to occur. Thus, if there is more food in an area, they will be more chance to divide as there is a food source for other bacteria. Cell division in prokaryotes happens rapidly and is a result of external factors such as nutrient levels.

What are the stages of binary fission in bacteria?

Week 2 : Genetics lesson 1 the cell cycle and mitosis

       

The DNA must be copied-this is usually a single stand of circular DNA. The bacteria have to regions the ori-orgin and ter-terminus. The DNA is replicated when the DNA goes through a replication complex of proteins. As the dna replicates anabolic metabolism occurs which results in cell growth. When the replication of DNA is completed the DNA is separated at opposite ends. The ori regions move towards opposite ends of the cell, aided by special proteins. The bacteria have machinery that latch on to the DNA and separate it to the new daughter cells. The cell division completes with cytokines.

Explain the process of Cytokinesis in prokaryotic cells -

Cell wall pinches inwards to form a ring of fibres and major components called Ftsz. As the membrane pinches inwards, a new cell wall is formed. Thus, the two cells are separated.

Eukaryotic cell division Cells in eukaryotes divide with an organism. Not all, cells divide. There is more DNA in eukaryotes which can lead to more errors occurring.

Events of the cell cycle Reproductive signal -> dna replication -> segregation -> cytokinesis.

Reproductive signal -

Eukaryotic cells do not constantly divide whenever environmental conditions are adequate.

Week 2 : Genetics lesson 1 the cell cycle and mitosis -

In eukaryotic organism the reproductive signals are not usually related to the environment of a cell but rather to the function of the entire organism.

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Dna replication is usually limited to a certain part of cell division.

Replication

Segregation -

Newly replicated chromosome are sister chromatids. Separated during mitosis into new nuclei.

What is the cell cycle of eukaryotic cells? What is a cell cycle? A cell cycle is a period from one cell division to the next The cell cycle is split into mitosis/cytokinesis and interphase.

What are the stages of Interphase-this is the stage of DNA replication? 

Interphase is split into 3 parts G1, S-phase and G2 Interphase

G1 -8hrs

s -phase 4hrs

G2 – 1 hr

Week 2 : Genetics lesson 1 the cell cycle and mitosis Few cells will be in mitosis or cytokinesis most will be in interphase.

Key facts A chromosome is a dna molecule in the cell, and when the cell is in mitosis the chromosome is complexed with proteins to produce a visible, condensed structure. A chromatid is a dna molecule complexed with proteins that is the product of s phase dna replication. Chromatids are in pairs and lie attached to one another via the centromere until anaphase of mitosis.

Explain the stages of Interphase   

In interphase the nucleus is visible and cell functions including DNA replication occurs. Begins after cytokinesis and ends when mitosis starts. Most of the cells spend most of their time in interphase. DNA is replicated in interphase.

During interphase, the cell grows, and DNA is replicated

What are the phases of interphase?  

G1: between cytokines and the s phase, chromosomes are single, unreplaced structures. Duration of the G1 phase varies.

Variation in the time spent in g1 is why the cell cycle varies in organisms.  

The cell that never go past g1 phase go to a resting phase which is known as G0. Such as neuron cells in the brain. G1 is the normal cell stage.

Cells most likely to be in G1-biggest part. in the G1 phase there is no cell division. Then the cells get a signal which allows them to go to the s phase of interphase. Before they go to the s phase, they must pass the restriction point then cell is committed to cell division after this point onwards.

What is the G1-to-S transition?   

At the g1-to-s transition the commitment to DNA replication is made. The cell has therefore passed the restriction point. This occurs when the cells receive a signal from the surrounding to go to s-phase.

Week 2 : Genetics lesson 1 the cell cycle and mitosis

In the S phase, DNA replication results in the formation of identical pairs of DNA molecules, sister chromatids, that are firmly attached to the centromeric region

What is the S phase? During the S phase, DNA is duplicated into two sister chromatids, and centrosomes, which give rise to the mitotic spindle, are also replicated  

S phase: DNA replicates: sister chromatids remain together. G2: cells prepare for mitosis (they synthesis structures to move the chromosomes)

Specific signals trigger the transition from one phase to another. The cell fusion experiment allowed for these signals to be known.

Interphase is not part of mitosis. Most cells are in interphase.

Signals -What are the two regulatory proteins involved in cell cycle?

Two groups of proteins, cyclins and cyclin-dependent kinases (CdK), are responsible for promoting the cell cycle. Cyclins regulate the cell cycle only when they are bound to CdK; to be fully active, the CdK/cyclin complex must be phosphorylated, which allows it to phosphorylate other proteins that advance the cell cycle.

Week 2 : Genetics lesson 1 the cell cycle and mitosis    

The signals act through Cyclin-dependent kinases (cdk’s) The CDk’s are proteins molecules Protein kinases catalyse a transfer of a phosphate group from ATP to a protein (phosphorylation). Cdk is activated by binding to cyclin (allosteric regulation): this alters its shape and exposes the active site.

Extra info: MPF (maturation-promoting factor) is a cyclin- CdK complex that triggers a cell passage past the G2 checkpoint into the M phase.

What is a kinase A kinase is an enzyme that catalyses the transfer of a phosphate group from atp to a target protein-phosphorylation.

Experiment -

James maller at the university of Colorado Studied immature frog eggs. He found when he added a protein for maturing eggs that the latter were stimulated to divide. He called these proteins maturing promoting factors.

Week 2 : Genetics lesson 1 the cell cycle and mitosis

The cyclin is the protein that regulates the cdks.



CdK-s -transfer a phosphate from ATP. They are activated by cyclins which bind, causing a change in structure which allows them to bind to their target.

The binding of the cyclin to the CdK is a type of allosteric regulation. Allosteric regulation activates the CdK by altering its shape and exposing its shape and exposing its active site to substrates.



 Cyclins= regulate cell cycle  Cdks= are always present=inactive  Cyclin activates cdks. There are many different cyclin-cdks complexes acting at different stages of the cell cycle.

How do CdK work -

Cyclin CdK catalyse the phosphorylation of RB. Rb acts as an inhibitor of the cell cycle at the restriction point. For the s -phase to begin the cell must get past the RB block The CdK catalyse the phosphorylation of the RB molecule. Thus changes 3-d shape of RB.

Progress through the cell cycle is regulated by cdk’s thus must be regulated. Regulating CdK is done by regulating the cyclins. No cyclins = cdk’s are inactive. Cyclin-CdK act as cell cycle checkpoints. Interphase has three checkpoints.

What are the different signals in interphase 

G1- Cyclin signals start of cell cycle.

Week 2 : Genetics lesson 1 the cell cycle and mitosis  

S- signals DNA to replicate. G2 – signals protein synthesis.

What is the G1-S-transtion? Progress past the restriction point depends on retinoblastoma protein (RB). RB normally inhibits the cell cycle but when phosphorylated by G1-S cyclin-CdK, RB becomes inactive and no longer blocks the cell cycle.  

RB -----> RB-P (active-blocking cell cycle) ------->. Inactive -allows for cell cycle.

What happens In the G1 -cyclin E binds to CDK 2.  

CDK4 bounds to cyclin D this then activates RB. When RB is phosphorylated it cannot inhibit the cell cycle.

Cell cycle checkpoints A checkpoint is one of several points in the eukaryotic cell cycle at which the progression of a cell to the next stage in the cycle can be halted until conditions are favourable.

  

G1 -DNA damage The g1 check point checks to ensure everything is ready for cyclin to be produced. s- incomplete replication and DNA damage.

G2- DNA damage

The G2 checkpoint ensures all the chromosomes have been replicated and that the replicated DNA is not damaged before cell enters mitosis.

m- chromosomes unattached to spindle.

The M checkpoint determines whether all the sister chromatids are correctly attached to the spindle microtubules before the cell enters the irreversible anaphase stage.

Week 2 : Genetics lesson 1 the cell cycle and mitosis

Growth factors Growth factors are proteins made by cells that can travel to other cells, or act on the cells that make them, usually to stimulate cell division. Growth factors bind to specific receptors on target cells, setting off signal transduction inside the cell. This can lead to gene expression for cyclins e.g. cell cycle is stimulated.

Eukaryotic cells divide by mitosis A eukaryotic chromosome consists one or two linear chromosomes. Chromatin is the dna molecule associated with proteins called histones. Before the s phase each chromosome contains only 1 double stranded dna molecule. After s -phase it become 2 strands. In g2 the dna is held by cohesion. End of g2-proteins called condesions coat the dna making it more compact. Nucleosome; this is the dna-histone interactions and the histone-histone interactions.

Mitosis mitotic phase: replicated DNA and the cytoplasmic material are divided into two identical cells   

Newly replicated chromosomes are closely associated (sister chromatids) Mitosis separates them to two new nuclei Separating many large, linear chromosomes would be difficult.

   

Chromosomes condense to make separation easier. We have two copies of chromosomes (maternal and paternal) DNA molecules bind with proteins to make chromatin. Additional proteins condensins coat the DNA molecules to make them more compact.

Eukaryotic DNA molecules are extensively packed and organized by histones-proteins with positive charges that attract the negative phosphate groups of DNAs.

Mitosis ensures accurate segregation of chromosomes to daughter cells.

Week 2 : Genetics lesson 1 the cell cycle and mitosis Mitosis separates the chromatids and they appear as sister chromatids. In 1882 the German anatomist Walter Fleming developed dyes to observe chromosomes during mitosis and cytokinesis.

What are the phases of mitosis? Mitosis Prophase , Prometaphase



, Metaphase

, Anaphase

Prophase: chromatin condenses, and chromatids become visible.

During prophase, the nucleus disappears, spindle fibres form, and DNA condenses into chromosomes (sister chromatids).



Prometaphase: nuclear envelope breaks down and chromosomes attach to spindle.



Metaphase: chromosomes line up at the middle. The chromosomes are all lined up at the metaphase plate.



Anaphase: chromatids separate and move to opposite poles. In anaphase the sister chromatids separate and move along the kinetochores microtubules towards the opposite ends of the cell.



In anaphase the chromatids separate, and this controlled by m phase cyclin CdK.

The microtubules chorten by depolymerizing at their kinetochore ends. 

Telophase: nuclear envelopes reform, spindle disappears, chromosomes becomes less compact.

Centrosomes The spindle apparatus, mitotic spindle or spindle are microtubule structures that move sister chromatids apart in mitosis. The orientation of the spindle apparatus is determined by centrosomes. Centrosome is an organelle in the cytoplasm near the nucleus consists of pair of centrioles.

Week 2 : Genetics lesson 1 the cell cycle and mitosis During s phase the centrosome doubles at the beginning of prophase the two centrioles separate from one another moving to opposite ends. Thus, identifying poles for anaphase. The position of centrosome determines the orientation in which animal cell will divide. Thus, the relationships between the new cells. This is important for the type of signals the cells will receive.

What is the Spindle apparatus? The spindle apparatus moves sister chromatids apart:   

Made of microtubules -polymers of small proteins. Centrosome is an organelle near the nucleus. Orientation of microtubules but the centrosome an organelle near the nucleus.

Each centrosome consists of two centrioles-hollow tubes formed by microtubules at right angles. The centrosome doubles during s phase; during prophase, they move to opposite ends of the nuclear envelope.

Late in prophase, kinetochores develop on each chromatid. Kinetochores are proteins on chromosomes that attach microtubules from each pole moving them to equator of the cell.

What are the types of microtubules?     

 

Polar microtubules from a spindle framework, run from pole to pole. Kinetochores form later. Kinetochores microtubules attach to kinetochores on the sister chromatids and to microtubules in opposite halves of the spindle. The two sister chromatids in each chromosome pair become attached to kinetochore microtubules in opposite halves of the spindle. This ensures that the two chromatids will eventually move to opposite poles.

During anaphase, separation of sister chromatids in controlled by m phase cyclin-CdK: it activates anaphase -promoting complex (APC). Cohesion that holds the chromatids together is hydrolysed by separase at the end of metaphase.

Week 2 : Genetics lesson 1 the cell cycle and mitosis 

A non-functional cohesion would not allow close attachment of chromatids during cell division, and there would not be a centromere. The two chromatids would be separate and there would be no organization for kinetochore attachment. There would be ineffective segregation of one chromatid of a pair to each daughter cell.

After separation, the chromatids are called daughter chromosomes. Chromatids share a centromere Chromosomes have their own centromere.

What are Kinetochores? Kinetochores have motor proteins, energy from ATP moves chromosomes along the microtubules. Kinetochores microtubules also shorten, drawing chromosomes towards poles.

What is Cytokinesis?  

Cytokinesis is the division of the cytoplasm In animal cells the plasma membrane pinches in between the nuclei.

In animal cells cytokinesis occurs by a process called cleavage forming a cleavage furrow. 

During cytokines the two cells have a cleavage furrow in which the cells elongate allowing for them to divide. The cleavage furrow is made by actin filaments which are the contractile units.



In plant cells, vesicles from the Golgi apparatus appear along the plane of cell division. These fuse to form a new plasma membrane.



Contents of vesicles form a cell plate-the beginning of the new cell wall.

Thee cell plate is made of proteins and cellulose that are deliver to the cell plate from the cell wall. In plant cells a cell plate forms Golgi vesicle and this makes a new cell wall to separate the two daughter cells. Cell membranes grow below the cell walls.in animal cells microfilaments contracts to pinch off the cell membrane and the cells separate.

 

Following cytokinesis, each daughter cell contains all the components of a complete cell. Organelles such as ribosomes, mitochondria and chloroplasts do not need to be disturbed equally if some are present in each cell.

Week 2 : Genetics lesson 1 the cell cycle and mitosis Extra information Cell division can be trigged by external factors. . An event may be as simple as the death of a nearby cell or as sweeping as the release of growth-promoting hormones, such as human growth hormone (HGH). A lack of HGH can inhibit cell division, resulting in dwarfism, whereas too much HGH can result in gigantism. Crowding of cells can also inhibit cell division. Another factor that can initiate cell division is the size of the cell; as a cell grows, it becomes inefficient due to its decreasing surface-tovolume ratio. The solution to this problem is to divide

Summary of cell cycle events Interphase G1: growth, restriction point ends S: DNA replication G2: spindle synthesis begins, preparation for mitosis

What is Mitosis? Prophase: condensation of chromosomes, spindle assembly Prometaphase: nuclear envelope breakdown, chromosome attachment to spindle

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Metaphase: alignment of chromosome at equatorial plate. Anaphase: separation of chromatids, migration to poles.

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Telophase: chromosomes decondense, nuclear envelope re-forms Cytokinesis: cell separation, cell membrane and or wall formation.

P16 blocks interactions of cyclin and it’s CdK that act at the g1-s boundary.

Week 2 : Genetics lesson 1 the cell cycle and mitosis

Key facts



somatic cell: any normal body cell of an organism that is not involved in reproduction; a cell that is not on the germline



Matched pairs of chromosomes in a dip...


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