CYTOGENETICS

4 - CELL CYCLE: MITOSIS AND MEIOSIS (PART 1)

Angelo Jayson Uy, M.D | February 6, 2023

TOPIC OUTLINE
I. TOPIC 1 IV. TOPIC 4
II. TOPIC 2 V. TOPIC
III. TOPIC 3

CELL CYCLE

Cell division is a process that includes nuclear division and

cytoplasmic division.

Cytoplasmic division - Cytokinesis

Nuclear division - Karyokinesis
- Mitosis
- Meiosis
2 Mechanisms

➔ Mitosis
◆ Cells division is somatic cells
◆ Muscle, White blood cells
◆ Non-reductiona l/ Equational
● Parent cell and daughter cell (when
you compare them together after
undergoing mitosis) both cells would
have the same amount and the same
quality of the genetic component. Cell cycle is divided into 2 phase:
➔ Meiosis ● Interphase
● Cell division in developing germ cell in the - from G1 phase to G2 phase
ovary and the tests - It is the phase of the cell cycle when the
● Reductional cellular components are replicated not only just
- Products have approximately half of the DNA, the cellular organ is also therein.
the genetic material as the parent cell ● Mitosis
- It is in mitosis when the cell distributes its
contents into the daughter cell.
● G0 phase
- A particular phase in cell cycle wherein the cell
will be able to discern if there's a need to
proceed with cell division or remain in its
specialization.

INTERPHASE

is the metabolically active non-dividing stage of the cell cycle

because before a cell can enter cell division, it needs to take in
nutrients. Cell division in itself is a very energy expanding
process. All of the preparations are done during the interphase
which involves a series of changes that takes place in a newly
formed cell and its nucleus before it becomes capable of cell
division.

● Before a cell can enter cell division, it needs to take in

nutrients
● All of the preparations are done during interphase
● Interphase is a series of changes that takes place in a
newly formed cell and its nucleus, before it becomes
capable of division again.
This governs the ability of the cell and its capability of deciding to ● 90% of the life of cell
proceed with cell division, if there's a need to divide, like into 2 - Either magpatuloy sa kanyang work or ipadami
daughter cells so on or stay quiescence for a while, or undergo ang self niya. Pero dun siya sa ipadami sarili
program cell death or apoptosis. nya.

Interphase proceeds in three stages, G1, S, and G2…

- G1 - The biosynthetic activities of the cell;

● Growth / Gap
● Metabolic roles

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 CYTOGENETICS
4 - CELL CYCLE: MITOSIS AND MEIOSIS (PART 1)
Angelo Jayson Uy, M.D | February 6, 2023

● In this phase the cell would prepare itself. ◆ Kinesin and Dynein - microtubules within the
● Making sure if the DNA is ready for replication spindles.
● 25% Kinesin allow movement towards the end for
- From 90%, 25% is dito. adding subunits. TAGA-TULAK
Dynein causes movement towards the less
- S - starts when DNA replication commences active end for removing subunits. TAGA-HILA
● Synthesis ➔ Followed by the breakdown of the nuclear membrane
● Starts when the DNA replication commences which marks the end of prophase
● Phase where actual replication happens
● 40%
- G2 - Accumulation of energy for Mitosis
● Growth / Gap
● Involves other accumulation of energy for
mitosis.
● 25%

MITOSIS also has phases

- This is the cell that undergoes prophase. Dahan-dahan

magdegrade ang nuclear membrane.
- Chromosomes have undergone condensation and
formed sister chromatids
- Would duplicate and appear as X
- Initial formation of microtubules forming mitotic spindles
- Centromeres displace towards the opposite ends of the
cell
MITOSIS
2. METAPHASE
- Mitotic division results in 2 daughter cells possessing
➔ Alignment of chromosomes in the same plane in the
identical copies of the genome of the parent cell
middle of the cell to form the equatorial plate
- Occurs in somatic cells (ALL cells except gametes)
(metaphase plate)
- 10% of the life of the cell
➔ Allow chromosomes to position in a single file
arrangement
Early 1920s
➔ Chromosomes move to metaphase plate and form
- Geneticist used cells from females most of the type and
single file arrangement with the help of microtubules
described them to help in reproduction. Hence, most
terms are mother cells, sister chormatids, etc.

4 STAGES OF MITOSIS
➔ Prophase
➔ Metaphase
➔ Anaphase
➔ Telophase

1. PROPHASE
➔ Chromosomes continue to condense becoming shorter
and thicker
Prometaphase
◆ Chromosomal condensing already happens even
➔ Centromeres already produce the mitotic spindles
before prophase
➔ Chromosomes still trying to arrange in a single file
➔ Centrioles replicate & migrate to the opposite poles of
➔ Still part of metaphase
the cell
➔ Mitotic spindles are formed: (come from centromeres
Metaphase
and are composed of protein subunits called:
➔ Chromosomes arranged linearly in a single file
◆ α and β tubulin - mitotic spindles that maintain
shape and structure of the cell and allow the
movement of cells internal components esp.
chromosomes

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 CYTOGENETICS
4 - CELL CYCLE: MITOSIS AND MEIOSIS (PART 1)
Angelo Jayson Uy, M.D | February 6, 2023

➔ Chromosomes uncoil; nucleoli are reformed together

with the nuclear membrane
➔ Constriction of the cytoplasm midway, cleavage furrow
deepens until it encounters the spindle, the microtubule
of the spindle depolymerizes
➔ Retract until separation into 2 daughter cells

➔ Kinetochore - holds sister chromatids together

➔ Microtubules come from centromeres

● Aster Microtubules - hold centromeres in place at polar

regions
● Polar Microtubules - help hold chromosomes in place
and other organelles, but focus on chromosomes
● Kinetochore Microtubules - connected to kinetochores
of chromosomes

3. ANAPHASE
➔ There is separation of the single kinetochore of each
pair of chromatids into 2
➔ The sister chromatids are free to move to opposite poles
of the spindle ● So, nabingwit na ng centromere nato itong mga
● The spindle separates the chromatids into two chromatids nato at nandito na sila sa particular
phases, we have the Anaphase A and polar region. Then, magkakaroon ng cleavage
Anaphase B furrow, at the same time the nuclear membrane
● Anaphase A - the chromosome moves will be reformed housing the chromosomes inside
towards the poles through the kinetochore as a and they will decondense forming this originally
microtubule motor decondense structure. Because diba kanina, the
● Anaphase B - the spindles are elongate and condensed form of chromosome is two
the rest of the chromosomes are pulled apart chromatids, since they have already gone cell
division, there is no need for a recondensation,
magdecondense yan sila and they would assume
this particular structure. You would end up now
with two diploid cells.

SUMMARY:

● Essentially, ito ang nangyayari: Bibingwitin

nitong mga kinetochore microtubules nato na
nakaattach sa mga kinetochores na ito. So
once anaphase ensues, hihilahin itong mga
chromosomes nato. This particular
chromosome will be pulled towards the pole
region where it is connected. So, kanya-kanya
yan sila ng bingwit ng chromatids and they are ➔ Here in the metaphase,
holding those chromatids at the kinetochore ● Formation of metaphase plate
with the use of kinetochore microtubules ● The chromosomes are aligned in a single row
produced by the centromeres in their ● There are the respective kinetochore
respective polar ends. microtubules already attached to the
kinetochores of each chromosomes
4. TELOPHASE ➔ In Anaphase
➔ Chromosomes are clustered at the spindle poles and ● The chromosomes are pulled towards polar
segments of the nuclear envelope are formed around regions depending on where they are
them. connected.
➔ In Telophase
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 CYTOGENETICS
4 - CELL CYCLE: MITOSIS AND MEIOSIS (PART 1)
Angelo Jayson Uy, M.D | February 6, 2023

● The pulled chromosomes on their respective ● Liver Cells

polar ends, a nuclear membrane will reform - In G0, but can be “called back” to cell
and a cleavage furrow will also form from the cycle by external cues
microtubules ● Nerve and Muscle cells
● polar microtubules - aside from providing - Highly specialized
motility of the cellular organelles, they would
also provide structural integrity of the daughter - Arrested in G0 and can never divide
cell. They will form the cleavage furrow,
eventually separating into two individual CELLS BASED ON THEIR PROLIFERATIVE ACTIVITY
daughter cells (diploid). ❖ Static cell population/Permanent
➔ Cells no longer divide (nerve and cardiac
muscle cells) or rarely divide (smooth and
skeletal muscle cells) = stays in G0
➔ They have very very little mitotic activity to the
point na hindi talaga nila kaya magundergo ng
cell division

❖ Stable cell population/Quiescent

➔ Little mitotic activity but are able to divide
during repair (fibroblasts, osteoblasts,
Electron Micrograph of cleavage furrow hepatocytes)
➔ They undergo cellular division only in the
presence of some form of disintegration in the
tissue structure that would need repair.
➔ Ex. fibroblast are seen in the wounded site -
INTERPHASE there is a disintegration of the cells of the skin
so the fibroblasts would undergo a cell division,
providing a fibrous scar allowing the
maintenance of the cellular lining of the skin.

❖ Continuously dividing cells/Labile

➔ Regular mitotic activity
(erythrocytes/leukocytes, epithelial cells of skin
and mucous membranes)
➔ Constantly goes through the cell cycle,
sometimes not even passing the G0 phase.
➔ Ex.
● To maintain the structural integrity of
the skin, they have to constantly
undergo cell division,
● The mucous membranes of the
stomach or gastrointestinal lining are
always exposed to the harmful effects
of the hydrochloric acid so aside from
➔ In this particular phase in the cell cycle, a very integral
producing mucus to coat the
part has to be accomplished deciding whether the cell
gastrointestinal tract, the cells
will just remain quiescent or would undergo cell division
themselves would be worn out and
or will undergo apoptosis.
some of the cells that would not get
➔ There are a lot of growth factors or protein factors that
worn out would undergo cell division
would help in regulating this interphase.
to replace them.
● If you have relatives or friends
1. G0 PHASE undergoing chemotherapy, the
chemotherapeutic agents attack these
particular type of cells, the cells that
would almost always undergo cellular
division. For the reason that, we have
not developed a certain type of cancer
therapy that would just target the
cancer cells specifically. It is a
shotgun approach wherein all of the
cells that would constantly undergo
cell division which primarily be the
cancer cells (because cancer cells
have unregulated cellular division) are
➔ Resting phase the target. But along the way, other
➔ non -dividing, differentiated state (a cell that would not cells normally having regular mitotic
undergo cell division) ability are also affected.
➔ Most human cells in G0 phase
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 CYTOGENETICS
4 - CELL CYCLE: MITOSIS AND MEIOSIS (PART 1)
Angelo Jayson Uy, M.D | February 6, 2023

● The common symptoms of a patient of the protein itself. Hence,

undergoing chemotherapy is alopecia for its active site to be used
or hair loss because the cells in the in exerting its effects in
skin that are responsible for producing initiating the process of
hair follicles are affected because mitosis, iot should not have
these cells undergo constant mitotic any phosphate group
activity. Also nausea and vomiting attached to it.
because the epithelial cells of the ■ CSC2P needs one cyclin
mucous membranes are also affected. (Cyclin B) for it to be an
active complex and exert its
effects

CONTROL OF THE CYCLE ➔ Cyclin-dependent Kinase (CDK)

● Dependent on a particular cyclin (specifically
Cyclin B) to exert its enzymatic effects in
initiating the transition from the G2 phase to the
M phase
● Initially, when the cell undergoes the G1 phase.
There is a presence of an inactive CDC2P.
Once it will slowly transition to the S phase,
Cyclin B (which is initially broken down from the
previous cycle) will accumulate.
● Inactive CDC2P and build up of Cyclin B would
form a complex through phosphorylation. It will
be an active complex once the inactive CDC2P
has undergo dephosphorylation to remove
phosphate in the active site

➔ Anahase-Promoting Complex (APC)

● Another existing regulatory factor that will
disintegrate the complex, halting the process of
mitosis because it has to occur at some point. It
can’t be forever going through mitosis.
Otherwise, we are talking about a cancer or
➔ There are regulatory factors that govern the cell cycle
neuroplasia.
➔ Maturation/Mitosis Promoting Factor (MPF)
● This is a protein complex that initiates mitosis
CHECKPOINTS
phase of the cell cycle
● Made up of 2 proteins:
○ Cyclin B
○ Cdc2p (cell division cycle to
protein)
○ Cyclin B oscillating in a month
○ CDC2P remains constant in a month
and it is a kinase in which it controls a
particular process wherein the
process of phosphorylation is used to
control the process of transitioning
from G2 to mitosis. It needs some
form of phosphorylation, this involves
a transfer of a phosphate group from
adenosine triphosphate to an amino
acid of the protein it is acting upon (in
this case the CDC2P)
○ Phosphorylation controls many
processes in mitosis and metabolism
in general
○ Example of phosphorylation ➔ There are checkpoints that allow the cell to make sure
■ Breakdown of a nuclear the events are properly completed
membrane when its protein ➔ Per checkpoint, there is a cyclin-dependent kinases that
subunits are phosphorylated govern them
○ The existence of CDC2P is governed ➔ G1/S checkpoint
by phosphorylation ● Proper cell size and DNA damage checking
○ CDC2P cannot initiate its effect in ➔ G2/M checkpoint
transitioning towards mitosis for 2 ● DNA replication completion and damage
reasons: checking
■ CSC2P has phosphate group ➔ M checkpoint
wherein the phosphate group ● Proper spindle fiber assembly and attachment
is attached in the active site

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