CELL CYCLE

• An orderly sequence of events that take place in a cell leading to duplication of its DNA (DNA replication)
and division of cytoplasm and organelles to produce two daughter cells

BINARY FISSION (PROKARYOTIC CELLS)

1. The bacterium before binary fission is when the
DNA is tightly coiled.
2. The DNA of the bacterium has uncoiled and
duplicated.
3. The DNA is pulled to the separate poles of the
bacterium as it increases the size to prepare for
splitting.
4. The growth of a new cell wall begins to separate
the bacterium, often with a "Z-ring" form by the cytoskeleton FtsZ
5. The new cell wall fully develops, resulting in the complete split of the bacterium.
6. The new daughter cells have tightly coiled DNA rods, ribosomes, and plasmids; these are now brand-new organisms.

RESTING GAP 0 G0 A phase where the cell has left the cycle and has stopped dividing.
INTERPHASE GAP 1 G1 Cells increase in size in Gap 1.
The G1 checkpoint control mechanism ensures that everything is ready
for DNA synthesis.
SYNTHESIS S DNA repication occurs during this phase.
GAP 2 G2 During the gap between DNA synthesis and mitosis, the cell will continue to grow.
The G2 checkpoint control mechanism ensures that everything is ready to enter the
M (mitosis) phase and divide.
DIVISION MITOSIS M Cell growth stops at this stage and cellular energy is focused on the orderly division
into two daughter cells. A checkpoint in the middle of mitosis (Metaphase
Checkpoint) ensures that the cell is ready to complete cell division.

INTERPHASE
• a series of changes that takes place in a newly formed cell and its nucleus before it becomes capable of division
again. Typically, interphase lasts for at least 91% of the total time required for the cell cycle.
Interphase proceeds in three stages, G1, S, and G2, followed by the cycle of mitosis and cytokinesis. The cell's
nuclear DNA contents are duplicated during S phase.
1. G1/GAP 1 (growth phase)
• The cell increases its supply of proteins, increases the number of organelles (such as mitochondria,
ribosomes), and grows in size.
• Cell is active in biochemical level
• 3 exits:
i. To continue cell cycle and enter S phase
ii. Stop cell cycle and enter G0 phase for undergoing differentiation.
iii. Become arrested in G1 phase hence it may enter G0 phase or re-enter cell cycle.

G0 is a resting phase where the cell has left the cycle and has stopped dividing.
- Cell cycle start with this phase
- The word "post-mitotic" is sometimes used to refer to both quiescent cells (INACTIVE)and senescent
cells (DNA damage and external tress).
2. S/ Synthesis
• Starts when DNA synthesis commences
• Rates of RNA transcription and protein synthesis are very low during this phase except HISTONE
production
• 46 chromosomes = 96 chromatids
3. G2/ GAP 2 (growth phase)
• occurs after DNA replication
• is a period of protein synthesis and rapid cell growth to prepare the cell for MITOSIS
• microtubules begin to reorganize to form a spindle
CONTROL OF THE CELL CYCLE
I. MECHANISMS
A. EXTERNAL
• PROMOTION
• Death of a nearby cell
• Release of Human Growth Hormone
• SIZE of the cell
• INHIBITION
• Crowding of cells
B. INTERNAL - 3 CYCLE CHECKPOINTS
1. G1 Checkpoint - determines whether all conditions are favorable for cell division to proceed:
- Check for genomic DNA damage
- Adequate reserves and cell size
- Also called RESTRICTION point – a point at which the cell irreversibly commits to the cell division process.
Either the cell could start repairing to proceed to G0
2. G2/M Checkpoint - Ensures that all of the chromosomes have been replicated and there is no DNA damage
- if problems are detected with the DNA, cell cycle is halted and the cell will attempt to either
complete the DNA replication or repair the damaged DNA.
3. Metaphase/M Checkpoint
- Also known as SPINDLE checkpoint
- It determines whether all the sister chromatids are
correctly attached to the spindle microtubules
- Kinetochores of each pair of sister chromatids are firmly
anchor to at least two spindle fibers arising from the
opposite poles of the cell
• CENTROMERE is a point of constriction on the chromosome containing repeated DNA sequences that bind
specific proteins.

• KINETOCHORE is a disk-like structure protein complex that functions as an attachment site for microtubules
necessary to separate the chromosomes during cell division.

II. REGULATOR MOLECULE

A. POSITIVE REGULATION – promote cell cycle
1. CYCLINS - 4 cyclin proteins fluctuate throughout the cell cycle in a predictable pattern
o Can regulate only when tightly bound with Cdks. Cyclin is a regulatory protein required to activate CDK.
o To be fully active, it must be phosphorylated in specific location
o After the cell moves to the next stage of the cell cycle the cyclins that were active in the previous stage
are degraded

2. CYCLIN-DEPENDENT KINASES - CDK is a protein kinase that activates numerous cell proteins by
phosphorylating them. Also, give the ‘go-ahead’ signals at the G1 and G2 checkpoints. The kinases that drive
these checkpoints must themselves be ACTIVATED. This complex is also called Mitosis Promoting Factor (MPF).
Phosphorylate – combine with phosphate/phosphoric acid

B. NEGATIVE REGULATION – halt the cell cycle

1. Retinoblastoma protein - a group of tumor-suppressor proteins common in many cells
• A group pf tumor suppressor protein
• Exerts its regulatory influence on other positive regulator proteins
• Monitors cell size
• Binds to transcription factors to “TURNOFF”
2. p53 - a multi functional protein . If damaged DNA is detected, p53 halts the cell cycle and recruits
enzymes to repair the DNA. If not, triggers APOPTOSIS (programmed cell death) to prevent the
duplication of damaged chromosomes
3. 21 - Enforces the halt in the cell cycle dictated by p53 by binding and inhibiting the activity of CDK/cyclin
complexes
• Exposure to stress, higher levels of p53 and p21 accumulate making it less likely that the cell will move into the S
phase.

• P53 and P21 refer to the functional molecular masses of the protein expressed in kilodaltons (p)