cell cycle - lecture 1 -

Important for replication  

Many therapies work through this method especially cancer drugs  

Cells take advice from surroundings on when to divide  

The reason embryo replicates the correct manner is due to the infromation from the cells around it – this is not an internal process  

cell replication is a large process

  1. Interphase:

    • G1 Phase (Gap 1): This is the first growth phase after cell division. The cell increases in size, synthesizes proteins, and prepares for DNA replication.- this phase the cell cycle accumulates the things it needs to make a new cell - it gets amino acids etc-

    • once the cell reliases it has enough material - it can then engage the cell cycle and start to synethsis the nucelotides to make dna

    • S Phase (Synthesis): DNA replication occurs in this phase. The genetic material is duplicated to prepare for cell division.- large number of cancer drugs aimed at this

    • G2 Phase (Gap 2): The cell continues to grow and prepares for mitosis. Organelles replicate, and the cell checks for DNA errors before entering the next phase. - checks all the dna to make sure its okay to continue to mitosis

  2. Mitosis:

    • Prophase: Chromatin condenses into chromosomes, the nuclear envelope breaks down, and spindle fibers form.

    • Metaphase: Chromosomes line up along the cell's equator, and spindle fibers attach to the centromeres of each chromosome.

    • Anaphase: Sister chromatids separate and are pulled toward opposite poles of the cell by the spindle fibers.

    • Telophase: Chromosomes reach the poles, the nuclear envelope reforms, and chromosomes unwind back into chromatin. Cytokinesis often begins in this phase, dividing the cytoplasm.

  3. Cytokinesis:

    • This is the final stage where the cytoplasm divides, creating two daughter cells with identical genetic information.

Microtubules:

  • Microtubules are dynamic, tube-like structures made of protein subunits called tubulin.

  • They form the cytoskeleton, providing structural support and serving as tracks for organelle movement within the cell.

  • During cell division, microtubules organize into structures known as the mitotic spindle.

Spindle Fibers:

  • Spindle fibers are a subset of microtubules involved specifically in cell division.

  • They form the spindle apparatus, a crucial structure for the proper segregation of chromosomes during mitosis.

  • Spindle fibers originate from two centrosomes located at opposite poles of the cell. They extend toward the center and interact with chromosomes.

Cytokinesis:

  • Microtubules also play a role in cytokinesis, the physical separation of the cytoplasm to form two daughter cells.

  • They help position the contractile ring, made of actin and myosin filaments, which constricts to divide the cytoplasm.

meoisis

this is a different form - important for replication to drive genetic variation

same proteins are important

there are 22 chromosones

  • mini chromosone maintanence proteins - these bind in before S phase or early G1

  • then when the cell is asked to replicate they all fire at once - you get replication of both chromosones at the same time

  • everything in the cell needs to be replicated -phosphorulation casacdes dicate this replication - there is phosuphorulation of proteins

the cyclin dependent kinases

these are the key proteins for this phosphurulation cascade

G1- CyclinD - CDK 4/6 - the synethissi of cyclin D determines whether the cell will undergo replication

Restriction Point - no return past this point - cyclin E - CDK -2 - synthesises new nucleotides for the new dna

S - cyclin A - CDK 2

G2 - cyclin A - CDK1

m - cyclin B - CDK 1 - this was first to be discovered

cyclin dependent kinases

they are a kinase - because they phosphorulate things - they are cyclin dependent because they require another protein ( cyclin) to activate them )

how they work

they take a terminal phosphate from atp - they stick this onto a protein substrate

this either activates the protein or inhibits the protein

how does cyclin associates activate the CDKs

  • structural requirements

  • the protein has two seperate domains - the n terminal domain has beta sheets and the c terminal has alpha helixes

  • the atp is not assesible - the cyclin gets made to move an alpha helix and change it to a beta sheet to make the atp accessible - this exposes the atp and then the kinase can phosphurlate many substrates - the supply of the cyclin determines if theyre active or not

the cyclin dependent kinases are serine theronine kinases

theres three aminoacids that get phosphrulated - serine - threonine - tyrosine

  • these three are used becasue each has a hydroxyl group that can be phosphurulated

  • the kinase can put the phosphate on to activate the protein

  • but also to a

the phosphoases - these remove the phosphate that the kinase placed

the cyclin depepndent kinases are serine theronine kinases - all of its subtrates are proteins phosphorulated serine and theronines

why use phosphate = its very quick - you need to progress through the cell cycle fairly quickly - phosphate easy to remove

the methods of control

  • production of cyclin

  • the phosphrulation

  • dephosphorulation

  • ubiquination - trashes the proteins

  • wee 1 - puts phosphate on cyclin - inhibits cell cycle

  • the cdc 25 phosohrtases are the enzymes that remove these phosphates and ensure that the cycle can go ahead - under normal circumstances they are inactive

ubiquitin - 76 amino acids long - when the cell wants to get rid of a protein - phosphurulates then trashes with the ubiquitin

there are three different enzymes

ubiquitin actvating enzyme - E1

Ubiquitin conjugating enzyme E2

ubquitn ligase

all together take the protein and put the ubquitin onto a lycine residue

the protein is then brough to a proteosome

degrades it into small peptides

this is a very energy dependent process - atp

ubiquitin can have other roles in the cells

can also traffic proteins

control trnaslation

dna can be damaged at any point - the phospharulases then stop this process straight away

the cell doesnt decide to replicate itslef - it takes this information from the cells around it and the receptors sense this

there are also inhibitory cell receptors

control of restriction point

controled by retina glastoma

cells can permantely leave the cell cycle -neurons