Cell Cycle, Cell Division and its Control Flashcards
what happens when cells divide
- They produce 2 daughter cells that are diploid and cell have a full set of chromosomes – mitosis
- Or they produce 4 daughter cells that contain only one copy of each chromosome they are haploid – meiosis
what are the 4 main phases of the cell cycle
- G1
- S
- G2
- M
- GO – non dividing, fully differentiated or quiescent stem cells, or not going through the cell cycle
How long does each part of the cell cycle take
- 23 hours spent in interphase
- 1 hour spent in mitosis
what phase does cell growth occur in
cell growth occurs in interphase and not mitosis
what is interphase made up of
G1
GO
S
G2
what is mitosis made up of
Prophase
Metaphase
Anaphase
Telophase
describe what happens in G1 and G2
- Gap (growth) phases – need to grow so they can make two cells out of one cell
- Longest phases
- No synthesis of DNA
- Cell has checkpoints and the cell will not progress unless they are met
- Replication of organelles happen in G1 and production of proteins, cytoplasm and nucleotides
- G2 – cell double checks DNA has been copied properly and checks for errors, if they are unable to repair errors then the cell undergoes apoptosis
- G1 - Cell checks the environment both internally and externally – make sure that the external environment is correct around the cell so it can receive the daughter cell
what is the interphase phase the cell spends most of the time in
G1 and G2
what happens in S phase
- Synthesis phase
- DNA is duplicated
- 2n to 4n – sister chromatids, each chromosome replicates
- chromosome are held at the centromere, so they are not mixed up at this point
- need 4N for two of the daughter cells
- semi-conservative replication
- this is where mutations can occur
describe mitosis
- division of the cell into 2 identical cells
what is cytokinesis
actual separation of the parent cell into two daughter cells
what happens in prophase
- DNA condenses to form chromosomes that are joint at the centromere
- Nucleoli disappears
- Nuclear envelope breaks down – chromosomes need to go into the main part of the cell,
- Centromere is a specialisation of the histones, this is an attachment point onto the microtubules
- Centrioles are special hollow structure that organise the microtubule assembly, organise mitotic growth spindles
- Centrioles separate and move apart towards opposite poles and organise the production of microtubule filaments
- Mitotic spindles start to appear and grow towards the equator of the cell
- Microtubules form a radiating array
- Chromosomes are attached to the microtubules by kinetochore
describe the structure of the kinetochore
- Contains two regions – inner region binds to the centromere and is assembled from specialised nucleosomes which are present throughout the cell cycle
- Outer region interacts with microtubules are only assembled during cell division
whats the role of the kinetochore
- attaches to the sister chromatids and pull the chromosomes apart, attached to the microtubules as well
describe the process of metaphase
- Chromosomes are lined up in the metaphase plate
- Centrosomes are at polar ends
- Microtubules and centromeres bind together to form kinetochores
- Kinetochore/microtubules are used to pull chromosomes apart, one from each pair of sister chromatids pulled towards opposite ends
- Cohesion are now only present in centromere to hold sister chromatids together
Describe the process of anaphase
- When chromosome reaches centrosome, the poles separate further by elongation of the polar microtubules
- Cohesin is hydrolysed and it is not functional anymore this allows separation
- they are pulled to polar ends
what are cohesinopathies diseases
- Cohesinopathies can lead to missing or extra chromosome in daughter cells
- Roberts syndrome
- Cornelia de lange syndrome
- Non disjunction of chromosmes – down syndromes meiosis I or ii
what holds the chromatids together
- Cohesin a protein holds sister chromatids together as they condense down
- There are enzymes that break down the cohesins except at the centromere so they can be pulled apart
- centromere
How do you get aneuploidy
don’t break down the cohesin therefore when pulling the chromosome apart can cause the microtubules to break and both chromosomes at one end and one daughter cell does not have the chromosome
describe telophase work
- Uncoiling of chromosomes
- Reformation of nuclear envelope
- Contractile ring forms of actin and myosin pinches the cell until it splits into 2 daughter cells , cytoplasm is dividing and division is completed
what is meiosis for
- Specialised for division for reproduction
- Leads to development of gametes
what does meiosis produce
produces haploid cells with half the number of chromosome
what are the two sections of meiosis separated by
interkinesis
What causes variation in meiosis
- Genetic material is exchanged between chromosome s
- Each gamete has different combination this produces genetic diverting
- crossing over (recombination)
where does crossing over take place
- Takes place in prophase 1 between homologous pairs of non-sister chromatids
- Crossing over of tails which is called chiasmata
How do we regulate cell cycle progression
- Cyclin dependent kinases (Cdks)
- Cdks are activated by cyclins
- Specific cyclin-Cdk complexes act at different parts of the cell cycle
- The combination of cyclins and CDKs produce energy required for the cell to progress to the next stage
what activated Cdk
cyclins active Cdk
how is an cDK activated
Cdk
- Breaks down ATP and releases a phosphsate
- phosphate given to substrate that binds to cyclic and activates Cdk
what can be a drugable target
cyclins and Cdk inhibitors to stop the cell going into the mitosis and replicating
what are the inhibitors for the Cdks
CKIs cyclin-dependent kinase inhibitors
why do we need inhibitors of Cdk
- stop cell cycle if the cell is not ready to go into the next stage
- give back control to the cell and stop it from replicating
How do CKI proteins work
- Bind to cdk’s to inhibit their function and negatively regulate cell cycle progression
- CKI proteins (p16, p21, and p27) primary act to block the entry into the cell cycle and the G1/S transition
describes what happens in retinoblastoma protein when CDK2 binds to it
P53 the tumour suppressor gene can control whether cyclin CDK2 can activate E2F
- CDK2 – causes the phosphorylation of Rb so it cannot bind to E2F
- E2F proteins continuously drive the cell cycle and they are the first gene directly linked to cancer
- E2F proteins activate mechanisms including S phase entry (for example by increasing cyclin expression) DNA synthesis and chromosome duplication
how does retinoblastoma lead to cancer
If the RB1 gene is mutated then a non functional Rb protein would be made
- Present in retinal cells
- Rb cannot bind to E2F
- E2F can enter S phase and have no control
- This leads to uncontrolled proliferation and cancer
what are the cell cycle checkpoints
1st - end of G1 - restriction point G1/S
2nd - end of G2(finished by end of G2) G2/M
3rd - metaphase - spindle checkpoint M
what are the 3 types of chemotherapy drugs (drugs used to control the cell cycle)
- Anti-mitotics
- biologics
- anti-hormonal drugs
describe how anti-mitotic work
- tradition chemotherapy drugs
- Anti-microtubule agents
- Affect all the dividing cells either tumour cells or human cells - non selective
There are two main classes - Vinca alkaloids prevent the formation of the microtubules therefore metaphase cannot occur
- Taxanes prevent the microtubule disassembly , chromsooems do not dissociate from the spindles and the cell cannot enter telophase
describe how biologics work
selective drug that target protein that are essential for their growth, monoclonal antibodies
- expensive
describe how anti hormonal drugs work
- Specific for hormonal driven tumours
- 2 functions – block hormonal production, block hormonal receptors
- E.g. breast cancer
what are the two classes of anti microtubule drugs
- Vinca alkaloids prevent the formation of the microtubules therefore metaphase cannot occur
- Taxanes prevent the microtubule disassembly , chromsooems do not dissociate from the spindles and the cell cannot enter telophase
Describe what the mitotic drivers do
- Other cell cycle inhibitors
- Inhibitors of mitotic kinases
- CDK inhibitors interfering with G1/S
- Aurora kinase inhibitors interfering with centriole/centrosome function
- Inhibitors of kinesins – microtubules motor proteins
- Other targets – cohesion and kinetochore
what is the cell cycle
- Cell cycle is the process by which a cell duplicates its genetic material (DNA) and divides itself to produce daughter cells
what is a kinetochore
a complex of proteins associated with the centromere of a chromosome during cell division, to which the microtubules of the spindle attach.
what is genetic recombination
- It is a process by which pieces of the DNA are broken and recombined to produce new combination of alleles
describe meiosis
Prophase 1
- Chromosome condense
- Nuclear envelope breaks down
- Crossing over occurs (recombination)
- Microtubules and proteins extend across the cell
- At the end of prophase the membrane around the nucleus of the cell erodes and the chromosomes are set free
Metaphase 1
- Pair of homologous chromosomes move to the equator region of the cell
- Each paired chromosome orientation is random, the random positioning helps diversify the cell
Anaphase I
- The meiotic spindle pulls the pairs of chromosomes apart
- Homologous chromosomes move to opposite poles of the cell
- Sister chromatids remain attached
Telophase and cytokinesis I
- Chromosomes gather at the poles of the cells and the cytoplasm divides
- They finish moving to their opposite poles
- Cytoplam pulls itself apart and 2 new daughter cells are formed
Meiosis II
Prophase II
- A new spindle forms around the chromosomes
- Chromosomes condense forming an X structure
- The membrane around the nucleus dissolves and chromosomes are released
- Centrioles duplicate themselves and the mitotic spindle is formed
Metaphase II
- Chromosomes line up at the equator
- Centrioles are at opposite poles of the cell
- Meiotic spindle attaches itself to each of the chromatids
Anaphase II
- Centromeres divide, chromatids move to the opposite poles of the cell
Telophase II and cytokinesis
- A nuclear envelope forms around each set of the chromosomes and the cytoplasm divides
- 4 gametes are produced with distinct genetic information
Describe check point 1
1ST check point (restriction checkpoint) Cell growth checkpoint (G1/S)
- Occurs at the end of G1
- Checks cell size, growth factors, DNA damage, nutrients
- Controlled by CKI, p16, which inhibits CDK4/6 so it cannot bind to cyclin D
- If not cell goes through resting phase until it was ready to divide
Describe checkpoint 2
2nd check point - DNA synthesis checkpoint – completed by the end of G2 (G2/M)
- Occurs end of G2
- Checks cell size, DNA damage, and DNA replication
- Uses a phosphatase to remove a phosphate from cyclin B/CDK 1 complex as the phosphate is acting as an inhibitor
- If there is damage to DNA, or incorrect replication the cell cycle would be stopped
- Cell continues onto mitosis
Describe checkpoint 3
Mitosis checkpoint – occurs during metaphase
- Spindle checkpoint
- Checks whether chromosomes are attached to spindles
- Tension in microtubules causes the initaiton of anaphase
- If so the cell divides and the cycle repeats
what are the two functions of antihormonal drugs
- block hormonal production
- block hormonal receptors
how does biologics work
- Selective therapy (monoclonal antibdoies)
- Selective targeting proteins essential for tumour growth
- 2 types – antibody drug cojugates – targets drug to tumour cells
- Antibodiy inhibitor of growth receptors
what are the two types of biologics
– antibody drug cojugates – targets drug to tumour cells
- Antibodiy inhibitor of growth receptors
what do rb proteins do
- Prevent cells moving past G1 phase
- Prevent cells entering s phase
- Prevents DNA synthesis and replication
- this is because they inhibit the function of the E2F protein
Name the cyclins and what they do
Cyclin D with CDK 4/6 - GO to G1 - G1 to S phase Cyclin E with CDK 2 - Prepares the cell for DNA replication Cyclin A with CDK2 - Activates S phase and DNA replication Cyclin A with CDK 1 - S phase to G2 Cyclin B with CDK 1 - G2 to go to mitosis
why do we need cell division
- Growth
- Make gametes
- Replace old cells that have undergone apoptosis
- Asexual reproduction
How does cytokinesis work
- Cytoplasm splits between the 2 cells
- Cell divides
what is the function of the cell cycle control
- Protein regulates whether the cell is ready to progress
- Checks whether the external environment is correct
what are chemotherapy drugs
these are drugs given in cancer to prevent uncontrolled growth
