The Cell Cycle Flashcards
The cell cycle consists of (2)
- Mitotic (M) phase (mitosis and cytokinesis)
- Interphase (cell growth and copying of chromosomes in
preparation for cell division)
Interphase (about 90% of the cell cycle) can be divided into subphases:
- G1 phase: first gap
- S phase: synthesis
- G2 phase: second gap
- G0 phase: resting phase, postmitotic quiescent
the first gap phase
G1 phase: first gap
Preparatory growth phase prior to cell entering DNA synthesis phase
G1
what cells are metabolically active during G1
- Requires nutrients & growth factors
- RNA, protein, lipid and carbohydrate synthesis occurs
Duration of G1. It is ____ in embryonic and cancer cells and __________ in rapidly dividing cells
Duration: variable (6-24hrs)
short and Rapid or non-existent
where DNA and chromosomal protein
synthesis occurs
Phase s
Duration of S phase
lasts approximately 7-8 hours in a typical mammalian cell with
a 16 hour cycle
In S phase, __________ are no longer needed. __________ occurs here, creating
two identical ______________
Growth factors no longer needed
DNA replication occurs here, creating two identical daughter genomes
what is second growth phase
G2
Interval between DNA synthesis (S phase)
and mitosis (M phase)
G2
synthesize of what occurs during G2 phase. Does cell growth continue?
enzyme, protein and ATP synthesis occur
yes, cell growth continues
Duration of G2
lasts approximately 3 hours in a typical mammalian cell with a 16-hour cycle
what is the mitotic phase where the cell undergoes mitosis and then cytokinesis?
What is the duration of this phase?
Mitotic phase
Duration: 1-2 hours
State of withdrawal from cell cycle. Cell is neither dividing nor preparing to divide
G0 phase
in what phase, is the cell described to be “doing its job” - performing its function within the tissue
G0 phase
Examples of cells in G0:
Hepatocytes, neurons
Checkpoints are based on a series of biochemical switches to initiate specific cell-cycle events.
cell cycle control system
Checkpoints are based on a series of ______________ to initiate specific cell-cycle events.
biochemical switches
Feature of the biochemical switches: Generally ______ (on/off) to launch an event in a complete & irreversible fashion
binary
what are the 3 features of biochemical switches?
- they are binary
- they are robust and reliable
- they are adaptable and modified to suit specific cell types
where are modifications to the cell cycle control system usually seen?
Cyclin dependent kinases (Cdks)
Points in the eukaryotic cell division cycle where progress through the cycle can be halted until conditions are suitable for the cell to proceed to the next stage
Checkpoints aka “Transitions”
Checkpoints can be regulated by:
- Factors within the cell, mostly controlled by the “health” or “state of preparation” of the cell
- Factors from outside the cell – i.e. messages from other cells within the same tissue or distant cells
Three major regulatory transitions at the:
- Start Transition (aka G1/S)
- G2/M transition
- Metaphase-to-anaphase transition (aka M-to-A)
For most cells, the ____ seems to be the rate-limiting and committing step of the cell cycle
G1/S
at every stage after this, the cell will either have to divide or it will die
what checkpoint would you ask: is the environment favourable?
G1/S
what checkpoint would you ask: is all the DNA replication? Is the environment favourable?
G2/M transition
what checkpoint would you ask: are all the chromosomes attached to the spindle?
Metaphase-to-anaphase transition (aka M-to-A)
Cdks are controlled a group of proteins called
cyclins
There are 4 classes of cyclins that form specific complexes with Cdks
- G1 cyclins: Cyclin D
- G1/S cyclins: Cyclin E
- S-cyclins: Cyclin A
- M cyclins: Cyclin B
Forms complex with Cdk4 or Cdk 6
Involved in G1 phase of cell cycle, needed for initiation of transcription of G1/S cyclins to help promote passage through start transition
G1 cyclins: Cyclin D
Cdks are responsible for cyclical changes in
_______________ of intracellular proteins that
initiate/ regulate the major events of the cell cycle
phosphorylation
Cyclical changes in cyclin protein levels result in the
cyclic assembly and activation of ________________ at specific stages of the cell cycle.
cyclin–Cdk complexes
- Forms complex with Cdk2
- Bind Cdk’s at the end of G1 & help trigger progression through start transition
- Levels decrease in S phase
G1/S cyclins: Cyclin E
- Forms complex with Cdk1 and Cdk2
- Bind Cdks after progression through start transition & helps stimulate chromosome duplication during S phase
- Levels remain elevated until mitosis; contributes to control of some early mitotic events
S-cyclins: Cyclin A
- Forms complex with Cdk1
- Bind CdKs to stimulate entry into mitosis at the G2/M transition
- Levels decrease in mid-mitosis
M cyclins: Cyclin B
Cyclin D and CDK 4 and 6 create which cyclin-cdk complex?
G1-CDK
Cyclin E and CDK 2 create which cyclin-cdk complex?
G1/S-CDK
Cyclin A and CDK 2 and 1 create which cyclin-cdk complex?
S-CDK
cyclin B and CDK 1 create which cyclin-cdk complex?
M-CDK
which cyclin-cdk complex is needed for progression through the start transition. What is it made up of?
G1-CDK - Cyclin D, CDK 4, and CDK6
which cyclin-cdk complex is needed to trigger progression through the start transistion. What is it made up of?
G1/S-CDK made up of Cyclin E and Cdk 2
which cyclin-cdk complex is to stimulate chromosome duplication and is involved in early mitotic events? What is it made up of?
S-CDK made up of the Cyclin A, CDK2 and CDK1
which cyclin-cdk complex is needed to stimulate progression through the G2/M checkpoint. What is it made up of?
M-CDK is made up of cyclin B and cdk 1
How do cyclin-Cdk complexes work?
Cyclins function by activating (phosphorylating) the Cdk
Cyclin protein does not simply activate its Cdk partner,
but also directs it to a specific target protein
Progression through the _____________ checkpoint is a little different
Metaphase-to-anaphase
the anaphase promoting complex (APC) is a member of what ligase family of enzymes
ubiquitin
What is APC used for?
to stimulate proteolytic destruction of specific regulatory proteins
What proteins do APC target for destruction?
securin, M-cyclins, S-cyclins
how does a Metaphase-to-anaphase checkpoint occur?
Occurs via regulated proteolysis
what happens when you ubiquitin something?
You target it for destruction
Ubiquitin is used to stimulate the proteolytic destruction of specific regulatory proteins
Early response genes are usually
usually transcription factors
Delayed response gene are usually
usually Cdks, cyclins, or other proteins needed for cell division
G1/S checkpoint: Active G1-cdk (and G1/S-cdk)
complex will target a protein called ___ and phosphorylate it
RB
RB functions as a transcription co-repressor. Hyperphosphorylation of RB will ___________ RB
inactivate RB
Inactive RB then releases a transcription factor E2F,
allowing transcription to proceed
Progression through G1 is delayed if:
- DNA is damaged by radiation, chemicals, or errors
- Absence of nutrients or growth factors
- Abnormal cell size
Entry into M is prevented when:
- DNA replication is not complete
- Presence of DNA damage
- Abnormal cell size
Progression through M-to-A is prevented if
Chromosomes are not properly attached to mitotic spindle
How is the cell cycle paused in unfavourable conditions? Two important molecular mechanisms:
- Cdk inhibitory proteins (CKIs)
- Proteins coded by tumour suppressor genes
what molecule is primarily used by cells to govern the activities of G1/Sand S-Cdks early in cell cycle
CKIs
Binding of Cdk inhibitory protein (CKI) inactivates cyclin-Cdk complex
CyclinD-cdk4 & CyclinD-cdk5 (G1-cdk complex) are inhibited by
p16
- CyclinE-cdk2 (G1/S-cdk complex)
- CyclinA-cdk2 & CyclinA-cdk1 (S-cdk complex)
- Cyclin B-cdk1 (M-cdk complex)
are all inhibited by
p21
- CyclinA-cdk2 & CyclinA-cdk1 (S-cdk complex)
- CyclinE-cdk2 (G1/S-cdk complex)
- Cyclin B-cdk1 (M-cdk complex
are all inhibited by
p27
p53 and RB are examples of
Tumour suppressor genes
what tumour suppressor gene recognizes and binds damaged DNA
p53
Unstressed cells have lower levels of p53 since it will be bound by a protein called Mdm2 and be degraded
what tumour suppressor gene is generally found in active form (hyperphosphorylated) and can recognize damaged DNA
RB