Cell division

- Mitosis: division of 1 parent cell into 2 genetically identical daughter cells. Occurs
when somatic cells proliferate.
- Meiosis: produces 4 gamete cells in reproduction.
- Does mitosis exist in bacteria? No mitosis occurs in bacteria, because in bacteria
materials are not divided equally, this is called mitosis.

- A mother cell: needs to accumulate energy => double the material in the cell => grow
=> divide.
- G1 phase: cells mature and grow (long)
- S phase: material duplicates in the cell (short)
- G2 phase: checks whether the replication process is occurring correctly or not (long)
- M phase: cell components divide evenly to both sides, mitosis (short)

- Mission:
+ Activate interphase processes
+ The mitosis process is quite well preserved => using Eukaryotic cells for
research
+ Signal
+ Protein interactions
- Proteins interact with protein kinases

- The bonds between amino acids in folded proteins are weak. When another protein
comes to interact with the target protein, a new bond will form, leading to the bonds
of the old folded AA being broken by the new protein, a new state will appear. =>
 Reveals new aa regions: serves as a binding site for other proteins, can expose the
enzyme active region, leading to that protein having enzymatic activity.
- Concept of motifs and domains in proteins
+ Motif: aa or dna string has a definite sequence => its function can be
predicted, those with repetitive components, for example: seeing an aa string
with a definite sequence, that string is specialized for attaching sugar
residues, proteins across the membrane 7 times,...
+ Domain: regions with different functions, e.g. a transmembrane receptor.
When folding, the domains will fold independently during the production of
drugs or recombinant proteins.

- Measuring Cdk of M phase, it was found that the protein concentration in the early
phases was low. Starting in M ​phase, M cyclin concentration peaked, then the
concentration decreased.
Control the concentration and activity of Cyclin Cdk
1) Ubiquitylation system: the process by which tagged proteins are sent to the
proteasome for degradation (a motif)

2) Phosphorylation and Dephosphorylation

- Phosphorylation is the addition of phosphate radicals, the interaction between the aa
of Cdk is changed => its active region is inhibited. The phosphorylated protein is
Wee-1. This process takes place at the beginning of M phase
- Dephosphorylation, the protein used is Cdc25 (phosphatase activity) to remove
phosphorus. When the phosphorus radicals are removed, Cyclin still exists. Cdk has
been removed to activate => interact with each other to push the cell into phase. M.
- Positive feedback

- Cdc25 is responsible for

dephosphorylation, pushing cells
into M phase.
- To be active, Cdc25 must be
phosphorylated to dephosphorylate
Cdk.
- It in turn phosphorylates Cdc25
phosphatase.
=> This process causes Cdc25 to
activate more, so this process is an
enhanced feedback process
(positive feedback).
- Processes take place based on
concentration, probability,...
- Is 100% of M-Cdk phosphorylated?
Are not.

3) Inhibitor protein
 - In an emergency, the inhibitor protein attaches to the complex causing inhibition.
- Protein p27 binds to M cyclin cdk and will inhibit the above process.
- Cell cycle under the control system

- First, the cell is in G1 phase, after the daughter cell is separated, it will accumulate
energy, creating new cell components, when it has stabilized, from G1 phase it will
move to S phase, but Before entering S phase, the cell will check the maturity and
integrity of the cell => In G1 phase, if the external environment is suitable (receives a
signal allowing the cell to mitosis), then G1 cdk begins. and G1S cdk will be activated
 and move the cell from G1 phase to S phase. At this stage, S cyclin begins to be
produced, however if the cell recognizes that the genomic DNA is broken, the
process is interrupted. This break will inhibit G1S cdk or S cdk, causing the cell to not
enter S phase. Only when the error is corrected can the cell enter S phase.
- When cells enter S phase, genome duplication takes place.
- When genomic DNA is duplicated, the G2 phase will check to see if the DNA has
been completely duplicated, if any chromosomes are not replicated normally, or if
they have been broken or edited. If the DNA is broken and has not been repaired, it
will not be allowed to enter M phase.

- Mitogen and cell division stimulation (Rb is a protein that inhibits cell division)
+ Mitogen binds to the mitogen receptor and activates G1-cdk and G1/S-cdk
with kinase activity. These two types will be responsible for phosphorylating
Rb protein. Rb protein will inhibit cell division.
+ When Rb is phosphorylated, transcription factors will be released that
transcribe, regulate, and express proteins used by the cell in the process of
DNA replication or cell replication.
- In the case of DNA breaks: a p53 protein will be kept at a certain concentration by
the cell. When the DNA is broken, the p53 protein is immediately phosphorylated =>
enters the nucleus, using itself for transcription. factor produces protein p21 (an
inhibitory protein) => p21 inhibits G1/S cdk and S cdk prevents Rb from being
phosphorylated and leads to no protein serving DNA replication => Cells do not move
enter the S phase cycle.
- If the p53 protein is mutated => the cell enters the S phase cycle => then the cell
copies DNA incorrectly => causing cancer.

- Eukaryotes must carry out the phosphorylation process to activate proteins such as
cdc6,...
- S cdk has a role in phosphorylation, activation of replication flying disc, and initiation
of DNA replication.
- When the chromosomes are formed, they will be attached to the spindle and divided
into two poles of the cell.
- Movement toward the equatorial plane is thanks to motor proteins
- The centromere is attached to the ends of a number of microtubule fibers located at
the equatorial plane

- The cohesin protein systemandcodensin ring: centromeres are attached to each

other thanks to protein rings => the role of cohesin and codensin ring
- Histone protein: helps coil and reduce the volume of chromosomes.
- Codensin ring: supports the process of maximum chromosome twisting.
- Cohesin: 2 sister chromosomes are attached to each other, keeping 1 always with 1',
2 always with 2',...
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stillagain ?
Role of cohesin and codensin ring

- Phase M cdk
+ Mcdk must be released and become active. Mcdk enters M phase, its task is
to activate the active APC/C process (ubiquitylation task). However, in this
step, APC/C does not ubiquitylate cyclin but does so for the Securin protein.
When entering the M phase checkpoint, APC/C is activated by Mcdk =>
APC/C will ubiquitylate Securin => decompose Securin => Separase is
released (Separase's task is to cut off cohesin rings) => Only 2 sister
chromosomes can go to the 2 poles of the cell.
 - In the middle of M phase, there is a checkpoint, all chromosomes must be attached
to the spindle before dividing to the two poles of the cell.
- Mad2: maintains a certain concentration in the cell, finds the centromere, attaches to
it, inhibits cdc20-APC/C => Securin is not inhibited => Separase is inhibited, the
cohesin ring is not cleaved, the cell is stationary .
*Cancer cells are cells that proliferate spontaneously=> inhibit separase or activate Mad
2
Mechanism of control points:
1. First checkpoint:
− Mitogen is a cell division signal that is transmitted asexually. This signal causes the cell to
begin transcription
and translation, moving cells from M phase to S phase.
− When there are no mitotic signals, the Rb protein (found in eye cancer cells) attaches to
the nucleus
Transcription factors inhibit transcription.
− When there is a signal from Mitogen, the Rb protein will be phosphorylated and
disassembled from the factor
Transcription helps the process of going into transcription.

2. Second checkpoint (checks cell damage and stops cells from entering S phase):
− Pro kinases detect DNA damage → kinases phosphorylate p51 protein → p51 binds
into the regulatory region of p21 protein → increased translation of p21 mRNA → p21 CKI →
inhibition
cyclin-Cdk prevents cells from entering S phase.

3. Control point 3:
− Mechanism that prevents duplication twice in one cycle: Pre-replication complex (Cdc6
+ additional pros) → At the end of G1 phase, S-cdk phosphirinizes Cdc6 → Complex
Pre-replicator is broken down, Cdc6 is destroyed → Transcription stops.
Mitosis is not completed unless all the chromosomes are attached to the spindle
cell division.

4. Control point 4: (control at the achromatic spindle)

− Mitosis is not completed unless all chromosomes are attached to the spindle
cell division.
− The mitotic checkpoint delays the transition to anaphase until all chromosomes are
attached.
− Prolonged activation of the checkpoint ® causes cell death.
⇒ Mechanism of many anti-cancer drugs.
- First force: elongation of microtubules and movement of protein motors.
- The second force: the negative direction slowly shortens at the two centrosomes,
pulling the chromatids closer to the centrosome