Cell cycle
● Interphase (G1, S and G2 phase)
● M phase ( mitosis and cytokinesis)
● Destinations
- Cells can go through differentiation where they will not go through mitosis, they
can take a pause from mitosis until there's damage or they can always go
through mitosis
Cell cycle control
● Checkpoints
● Use of checkpoints that make sure that cells are healthy and complete
● Include 3 checkpoints through cell cycle including
1. G1 checkpoint (is cell ready to do replication)
2. G2 checkpoint (was it replicated correctly)
3. M checkpoint (make sure that chromosomes line up correctly)
● Cyclin-cdk complexes
- Regulate cell cycle progression
- Cyclin must bind to cdk for it to be enzymatically active
- Cdk will always be there but it is not active until its specific cyclin binds and cdk is
phosphorylated
- All cdk complexes should be inactive by the end of mitosis
- 4 different cyclin complexes
1. G1-cdk (early G1 phase)
2. G1/S-cdk (late G1 phase)
3. S-cdk (s phase)
4. M-cdk (M phase)
Regulation of cdk-cyclin activity
● Cyclin must bind to cdk and cdk must be phosphorylated to be active
● Regulate cyclin-cdk by…
- inhibitory phosphate added by wee1 to cdk
- Cdk inhibitory protein (p27, p21)
- Cdk activating phosphatase that removes inhibitory phosphate added by wee1
(cdc25)
Starting cell cycle
● Going into G1 phase
- All cyclins destroyed by APC to reset cell after mitosis has finished
- Need Mitogen signal to remake cyclins through the Ras-MAPK pathway
- Activation of MAPK
1. Signaling molecule mitogen binds to RTK
2. RTK forms dimer and cross P
3. The Adapter (Grb2) has a SH2 domain that allows it to bind to RTK and
Ras-GEF. This makes Ras-GEF activated
, 4.Ras-GEF activates Ras by changing GDP into GTP
5.Ras activates MAPKKK(membrane bound effector)
6.MAPKKK acitvates MAPKK
7.MAPKK activates MAPK (2nd messenger)
8.MAPK will P transcription factors that will activate TR for cyclin D and E
9.This results in G1-Cdk and G1/S-Cdk that will P retinoblastoma (protein
that inhibits E2F) so releases E2F (activates TR for genes in S phase)
● Progression through G1
- Is the cell ready to replicate DNA
- Checkpoint 1: checks DNA for any damage
● If there is damage then cell cycle will be paused and repairs can be done
or cell will go through apoptosis
- If DNA is damaged then p53 will be activated and will be a TR factor that causes
p21 and p27 proteins to be transcribed and translated
- P27 inhibits G1-Cdks and p21 inhibits G1/S and S-Cdk
- This will pause the cell cycle and allow for any repairs to occur
● S phase
- If there was no damage or there were repairs done then go on to S phase
- DNA replication
● Prepare in G1 with E2F
○ DNA replication starts at origin of replication
○ The ORC complex will bind to origin to identify start site
○ Helicase binds at origin with ORC to unwind DNA. It gets
positioned at origin with the help of cdc6 that is bound to ORC
● S Phase
- S-cdk activates helicase in S phase by phosphorylating to start
replication
- Replication only needs to happen once so once it does then S-cdk
phosphorylates cdc6 and ORC so they don’t bind
- Centrosome duplication (mitotic spindle)
● G2 phase
- Checkpoint #2: replication is checked
- While replication is being checked, M-cdk is inactivated by wee1 by
adding a inhibitory phosphate to M-cdk
- When DNA replicated correctly then cdc25 will remove the phosphate
from M-cdk and move on to mitosis
M phase
● Mitosis
- Prophase
● Chromatin is condensed into chromosomes
- Chromatin is in non-dividing cells and can do TR. Chromosomes
are a condensed form of chromatin and no TR
- Condensin will condense chromatin by M-cdk P it
- Cohesion rings hold sister chromatids together
● Interphase (G1, S and G2 phase)
● M phase ( mitosis and cytokinesis)
● Destinations
- Cells can go through differentiation where they will not go through mitosis, they
can take a pause from mitosis until there's damage or they can always go
through mitosis
Cell cycle control
● Checkpoints
● Use of checkpoints that make sure that cells are healthy and complete
● Include 3 checkpoints through cell cycle including
1. G1 checkpoint (is cell ready to do replication)
2. G2 checkpoint (was it replicated correctly)
3. M checkpoint (make sure that chromosomes line up correctly)
● Cyclin-cdk complexes
- Regulate cell cycle progression
- Cyclin must bind to cdk for it to be enzymatically active
- Cdk will always be there but it is not active until its specific cyclin binds and cdk is
phosphorylated
- All cdk complexes should be inactive by the end of mitosis
- 4 different cyclin complexes
1. G1-cdk (early G1 phase)
2. G1/S-cdk (late G1 phase)
3. S-cdk (s phase)
4. M-cdk (M phase)
Regulation of cdk-cyclin activity
● Cyclin must bind to cdk and cdk must be phosphorylated to be active
● Regulate cyclin-cdk by…
- inhibitory phosphate added by wee1 to cdk
- Cdk inhibitory protein (p27, p21)
- Cdk activating phosphatase that removes inhibitory phosphate added by wee1
(cdc25)
Starting cell cycle
● Going into G1 phase
- All cyclins destroyed by APC to reset cell after mitosis has finished
- Need Mitogen signal to remake cyclins through the Ras-MAPK pathway
- Activation of MAPK
1. Signaling molecule mitogen binds to RTK
2. RTK forms dimer and cross P
3. The Adapter (Grb2) has a SH2 domain that allows it to bind to RTK and
Ras-GEF. This makes Ras-GEF activated
, 4.Ras-GEF activates Ras by changing GDP into GTP
5.Ras activates MAPKKK(membrane bound effector)
6.MAPKKK acitvates MAPKK
7.MAPKK activates MAPK (2nd messenger)
8.MAPK will P transcription factors that will activate TR for cyclin D and E
9.This results in G1-Cdk and G1/S-Cdk that will P retinoblastoma (protein
that inhibits E2F) so releases E2F (activates TR for genes in S phase)
● Progression through G1
- Is the cell ready to replicate DNA
- Checkpoint 1: checks DNA for any damage
● If there is damage then cell cycle will be paused and repairs can be done
or cell will go through apoptosis
- If DNA is damaged then p53 will be activated and will be a TR factor that causes
p21 and p27 proteins to be transcribed and translated
- P27 inhibits G1-Cdks and p21 inhibits G1/S and S-Cdk
- This will pause the cell cycle and allow for any repairs to occur
● S phase
- If there was no damage or there were repairs done then go on to S phase
- DNA replication
● Prepare in G1 with E2F
○ DNA replication starts at origin of replication
○ The ORC complex will bind to origin to identify start site
○ Helicase binds at origin with ORC to unwind DNA. It gets
positioned at origin with the help of cdc6 that is bound to ORC
● S Phase
- S-cdk activates helicase in S phase by phosphorylating to start
replication
- Replication only needs to happen once so once it does then S-cdk
phosphorylates cdc6 and ORC so they don’t bind
- Centrosome duplication (mitotic spindle)
● G2 phase
- Checkpoint #2: replication is checked
- While replication is being checked, M-cdk is inactivated by wee1 by
adding a inhibitory phosphate to M-cdk
- When DNA replicated correctly then cdc25 will remove the phosphate
from M-cdk and move on to mitosis
M phase
● Mitosis
- Prophase
● Chromatin is condensed into chromosomes
- Chromatin is in non-dividing cells and can do TR. Chromosomes
are a condensed form of chromatin and no TR
- Condensin will condense chromatin by M-cdk P it
- Cohesion rings hold sister chromatids together
