cell cycle helen filmore Flashcards
WHAT ARE THE STAGES OF THE CELL CYCLE and describe
INTERPHASE - cell growth. it is where most cells spend most of their time, except cancer cells
MITOSIS - active cell division
APOPTOSAIS
what are the phases of interphase and describe them
G1 = Growth phase, longest phase. cells organelles are made here such as ribosomes and proteins, and they all duplicate
S = Synthesis - DNA synthesis - so 23 pair chromosomes are duplicated to make 46 pairs
G2= prepare for mitosis by making microtubules
M= mitosis - cell divides into 2 cells
However, some cells go into G0 = no more cell division instead of S
what is mitosis
when the cell divides and produces 2 daughter cells
what are the phases of mitosis
prophase, prometaphase, metaphase, anaphase and telophase and cytokinesis.
DESCRIBE PROPHASE
- nuclear envelope start disappear
- centrosomes migrate to opposite ends
- DNA condenses
describe pro metaphase
- nuclear membrane is now gone
- chromosomes line up in the middle
- centrosomes are at opposite ends
describe metaphase
- centromeres form microtubules (aka spindle fibres) which extend to the each other and the chromatids
describe anaphase
the microtubules pull one chromatids of one type of chromosome to each other
- therefore, both microtubes have 1 chromatid of each of the 2 chromatid
- there is now 4 “chromosomes”
describe telophase
- cell dimples
- nuclear envelope begins to reform
- microtubules breaks down
describe cytokinesis
Cytoplasm divides- actin ring pinches cytoplasm along the crease of the two new cells- cleavage furrow.
two new cell forms
why are checkpoints important
they ensure various cellular conditions are met before proceeding to the next phase of the cycle
- they ensure that there are no DNA mutation or errors present which can potentially the passed down to future daughter cells
what happens if a cell has dna errors during checkpoint
- they stop the cell from entering mitosis so cell can fix error,
- if errors can’t be fixed, they cauuse cell to die by apoptosis
what are the check points for cell cycle to regulate them
G1/S phase checkpoint
G2/Mitosis checkpoint
Spindle checkpoint
which protein carry out these checkpoint process
- cyclin dependent kinases (CDK) - always present in a cell but their default is for them to be inactive
- cyclins - activates the cyclin dependent kinases
what are the types of cyclins
DEAB (in order )
what the types of cyclins and which phase are they produced in
G1 phase = Cyclin D , in which binds to CDK- 4 and CDK6
G1 / S Phase= Cyclin E in which binds to CDk2
S Phase = Cyclin A in which binds to CDK2
G2/M phase - Cyclin B which binds to CDK1
It’s reversed. Memorise order of DEAB and know it does from 4/6 - 1
D- cdk 4/6
E - cdk -2
A - cdk -2
B - cdk 1
what are the levels of cyclins like
their levels are cyclical. so all the cyclins are always present, but some are higher than others in different phases.
what is the check point for G1/S phase
- where cell chooses to proceed with S phase and divide or go into quiescence via the G0 phase
*it is mediated by Cyclin E/CKD2 complex and 2 cell cycle regulator proteins called Retinoblastoma protein (RB) and E2F
what does retinoblastoma protein do
+ it prevents excessive cell division by inhibiting cell cycle progression
+ apt signals for cell division are present such as cyclins, RB is inactivated by phosphorylation
What do CYCLIN E - CKD2 complex do ?
- it fully phosphorylates Rb (retinoblastoma protein) and INACTIVATES IT
- Rb is normally bound to a transcription factor E2F
- once Rb is phosphorylated, it releases E2F, so E2F is then able to bind the promotors of proteins required for cell division i.e dna polymerase and transition to S phase.
- it also phosphorylates P27 Kip 1, an inhibitor of cyclin D. Phosphorylation causes degradation of this protein which promotes expression of cyclin A.
- this allows the cell to enter S phase.
why is the RB and E2F protein so important (think cancer)
- if there is a mutation in the gene which codes for the Rb protein, you may have a complete loss of the inactivating role of the Rb.
- therefore, E2F will have nothing to bind to and will constant activate transcription for proteins required for dna replication and cell division
- as a result, cells with this mutation will constantly divide = cancer,
what is the G2/M check point
it ensures that any potential DNA errors / mutations that occurred in the S phase can be fixed before mitosis
what is the Spindle check point
occurs in mitosis , specifically between metaphase and anaphase. it ensures all of the chromosomes are positioned correctly.
what do the activated CKD2-CYCLIN A complex do
helps activate DNA replication as it allows entry into S phase.
* it ensures that DNA replication only occurs once.
what do the activated CKD4-CYCLIN D / CKD6 - CYCLIN D complex do
once G1 is initiated, cyclin D is synthesize and drives the G1 to s phase transition by forming the complex with CKD4
they partially phosphorylate a tumour suppressor protein called Rb, which is bound to E2F. when this is phosphorylated, it can’t inhibit DNA replication. an important factor for DNA replication,
what do the activated CKD1-CYCLIN B complex do
helps activate MITOSIS
what happens in the G1/S phase checkpoints
Cyclin E binds to CDK2
what are the types of mutations
1 point mutation = a single base pair is added, deleted or changed
- DNA amplification = here is an increase in the amount of DNA present in a specific region of a chromosome.
- chromosomal rearrangement
- epigenetic modifications such as methylation and acidification
what is the DNA damage response
it detects DNA lesions, signals their presence and promotes their repair.
what are the DNA damage response pathway
- Base excision repair
- nucleotide excision repair
- homologous recombination repair
- non homologous end joining repair
what is replication stress
slowing or stalling in replication fork progression
what is the progression through the cell cycle primarily controlled by
Proteins in the cytoplasm- Cyclins and Cyclin dependant kinases.
what changes in a cell causes uncontrolled cell growth
- activation of oncogenes such as RAS and MYC gene
- inactivation of tumour suppressor gene
what are tumour suppressor genes
they code for proteins which function to control cell division and ensure it only occurs when necessary
what happens when tumour suppressor genes are mutated
mutations lead to loss of function of tumour suppressor risk
this increases the risk of uncontrolled cell division
therefore increases risk of cancer
what are examples of tumour suppressor genes
P53
APC
BRCA1/2
what is the most important tumour suppressor gene to know
P53
what is the role of p53
in conjunction with other proteins, it ensures that only cells free of DNA errors can undergo cell division .
what does p53 do
it induces p21 for cell arrest
p21 is a protein which inhibits all cyclin -cdk complexes. without these complexes, the cell can not undergo cell division
what does p53 do in cells that contain DNA errors
> it will arrest cell division until the dna has been repaired
trigger proteins for dna repair
or trigger apoptosis of that cell
what happens when there is loss of p53
accumulation of dna mutations and eventually cancer.
what are oncogenes
RAS, gene
myc gene
what do RAS gene make and why is it important for DNA
RAS protein which is very important in cascades of MAPk proteins which will eventually activate a transcription factor. once these transcription factor are activated, they read the genes to make proteins for cell growth that allow the cell to go from G1 to S phase
what happens when there is a mutation in the RAS gene
RAS protein which are already activated and bound to ATP are formed.
- this causes continuous activation of the transcription factors
- therefore overproduction of proteins for cell division are formed
- cancer
what do MYC genes do
they make proteins in our body for cell growth, cell survival and cell activity
what does mutation in MYC gene do
cell becomes more cancerous so you get more cell growth, cell survival and cell activity
P16
Inhibits CKD 4/6
