Cell Cycle

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Central Dogma

Molecular Biology
Central Dogma of Molecular Biology

Components
1. DNA→ DNA
2. DNA→RNA
3. RNA→Protein
Central Dogma of Molecular Biology

Components
1. DNA→ DNA
2. DNA→RNA
3. RNA→Protein
4. RNA→DNA
Cell Cycle
Cell Cycle
Cell Cycle

A series of events that occur in a cell leading to its division and


duplication

A highly regulated process comprising:


Interphase, where the cell grows and replicates its DNA
Mitosis, where the replicated chromosomes are segregated into two
daughter cells
Cell Cycle

Cells destined to divide into two identical daughter cells normally


progress through a sequence of
1. Duplication of cell contents (Interphase)
2. Nuclear division (Mitosis)
3. Cytoplasmic division (Cytokinesis)
Cell Cycle
Interphase

Interphase
The period between cell divisions – Further divided into,
1. G1 [Gap1]
2. S [Synthesis of DNA]
3. G2 [Gap2]
G1 Phase (Gap1or First Growth)
G1 Phase
The initial stage of the cell cycle during which the cell
– grows
– carries out its specialized functions
– monitors its internal and external environment
– prepares for DNA replication and eventual cell division
Cell Cycle
S Phase (Synthetic Phase)
S Phase
A stage in the cell cycle where DNA replication occurs, resulting in
the synthesis of exact copies of the genetic material present in the
cell
Cell Cycle
G2 Phase (Gap2 or Second Growth)
G2 Phase
The stage in the cell cycle following DNA synthesis (S phase) and
preceding mitosis (M phase), during which the cell
– continues to grow
– synthesizes proteins
– prepares for cell division (by checking for DNA errors and ensuring
that all necessary components are in place for mitosis)
Cell Cycle
Mitosis
The process of nuclear division; further divided into
1. Prophase
2. Metaphase
3. Anaphase
4. Telophase – Cytokinesis
G0 Phase (Quiescent)
G0 Phase
A non-dividing state that some cells enter from the G 1 phase of the
cell cycle

Cells
– Temporarily or indefinitely cease cell division and proliferation
– Still maintain metabolic activity and perform specialized functions
G0 Phase (Quiescent)
G0 Phase
A non-dividing state that some cells enter from the G 1 phase of the
cell cycle

Cells (depending on various signals and environmental cues)


– Can re-enter the cell cycle under appropriate conditions OR
– Remain in the non-dividing state indefinitely
Cell Cycle Control
Check Points
Progression of cell cycle is controlled through an elaborate series of
check points, medicated by interaction between proteins,
1. Cyclins
2. Cyclin-Dependent Kinases (CDKs)
3. CDK-Inhibitors (CDKIs)
Check Points
Four Check Points at the:
1. G0 → G1 Transition
2. G1 → S Transition
3. G2 → M Transition
4. M Phases Transition
Control Mechanism
Example (Cyclins and CDKs)
Late in G1 Phase
– Cyclin D begin to rise and binds to constitutively expressed CDK4
and CDK6
– Cyclin D gets phosphorylated by CDK4 and CDK6
– Phosphorylated Cyclin D complexes with CDK4 or CDK6
– Cyclin–CDK complex phosphorylates nuclear Rb Protein
Control Mechanism
Example (Cyclins and CDKs)
Late in G1 Phase
– Phosphorylated Rb protein releases Transcription Factor (E2F) (Rb
protein normally binds and inhibits E2F)
– Free E2F initiates the transcription of genes required for cell cycle
progression
Control Mechanism
Example (Cyclins and CDKs)
Control Mechanism
Example (Inhibition)
Cyclin–CDK complexes can be inhibited by CDKIs. There are two
main families of CDKIs:
1. INK4 Family: Inhibitors of CDK4 (e.g., p16INK4a, p15INK4b,
p18INK4c, and p19INK4d)
2. Cip/Kip Family: Inhibitors of a broader range of CDKs (e.g.,
p21Cip1, p27Kip1, and p57Kip2)
Chemotherapeutic Agents (targeting cell cycle)
Drug Classes
1. Anti-metabolites (S): e.g., Methotrexate, 5-Fluorouracil
2. Topoisomerase Inhibitors (G1/S & S): e.g., Etoposide, Doxorubicin
3. Mitotic Inhibitors (M): Paclitaxel,Vincristine,Vinblastine
4. Platinum Compounds (G1 & S): e.g., Cisplatin
5. CDK Inhibitors: E.g., Palbociclib, Ribociclib

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