Genics
Long notes
, #Genetics
Q. Describe the Cell Cycle. Write in detail about the Apoptosis and its role in
health and diseases.
Cell cycle is the series of growth and development steps in a cell separated by gap phases.
Total duration of cell cycle ranges from 12 to 24 hrs.
Two phases -
lnterphase: preparatory phase; cell performs basic functions, replicates DNA
Takes b/w 18-20hrs
Mitosis: cellular division
Takes about 2hrs
GO(G-ZERO) PHASE
Cells function but not dividing/preparing to divide
Considered out side cell cycle
INTERPHASE
Three sub phases: G1,S, G2 phases :
Gap/Growth 1 (Gl) phase
Longest phase
Cell grows while organelles function as usual
Terminates with G1 checkpoint
Cells with damaged DNA G0 / apoptosis
Lasts upto 10hrs
Synthesis (S) phase
DNA replicated (identical chromatids created)
Last about 5-6hrs
Gap/Growth 2 (G2) phase
Organelles duplicated
Terminates with G2 checkpoint
Last about 3-4hrs
M PHASE (MITOSIS & CYTOKINESIS)
Cell divides into two daughter cells
Prophase – nuclear membrane breaks down
Prometaphase – replicated chromosomes are lined up
, Metaphase – chromosomes separated into 2 sister chromatids
Anaphase – chromatids arrive at ends of cell, decondense & form
separate nuclear membranes
Telophase – Plasma membrane pinches cell into 2
(G0 Phase = Some cells (neurons) that don't divide, just stop at G0 )
In cytokinesis, the contractile ring in the cytoplasm of the cell pinches the
mother cell in two, producing two new daughter cells.
Daughter cells may immediately undergo many rounds of cell cycle or remain
dormant till further signal for division.
The Cell-Cycle Control System / Checkpoints :
- A complex network of regulatory proteins that ensures a cell replicates properly
- The cell checks that all critical earlier events have occurred:
Eg: DNAreplication
Eg: Segregationofduplicatedchromosomes
- Responds to various signals from outside & inside the cell
- Critical to regulation of cell numbers
- Malfunction can lead to cancer (Abnormal number of chromosomes/Mutated DNA)
- Can stop the cycle using molecular 'brakes' at 2 important checkpoints
,G1 Checkpoint: DNA damage prevents S-Phase Entry:
- Ensures environment is favourable for cell proliferation
- Ensures DNA is intact before committing it to replication (S-Phase)
- S-CdK :
Damaged DNA causes expression of a Cdk Inhibitor Protein that inactivates the S-Cdk
S-Cdk is necessary for DNA replication in S-Phase
Therefore, inactivation of S-Cdk arrests the cell cycle in G1 phase
G2 Checkpoint: DNA damage prevents M-Phase Entry
- Ensures that cells don't enter mitosis until DNA replication is completed correctly
- M-Cdk:
Similar function to S-Cd in the G1 Checkpoint
S-Cdk is inactivated by phosphorylation & activated by dephosphorylation
If DNA is good, Phosphatase Cdc25 removes the inhibitory phosphor, instantly
activating the M-Cdk
If DNA is bad, phosphatase Cdc25 is inactive, & therefore so is M-Cdk
- Active M-Cdk further activates phosphatase Cdc25 & also stops the Cdk-inhibitory
kinase from adding the inhibitory phosphor →→ triggers MITOSIS
The Spindle Checkpoint
The M checkpoint is also known as the spindle checkpoint: here, the cell examines
whether all the sister chromatids are correctly attached to the spindle microtubules at
metaphase plate.
Cdc6:
Cdc6 is a regulatory protein that binds to ORC's (Origin Recognition Complexes) on DNA
Prevents DNA Replication until G1 checkpoint is satisfied
Activated S-Cdk removes Cdc6 via phosphorylation → allows DNA replication to continue
Rb-protein (Gene Regulatory Protein-B):
Rb-Protein is another regulatory protein that prevents gene transcription of S-Phase
proteins
Requires the presence of external growth-factors → intracellular cascade
Enzyme-linked receptor → Ras activated
Ras → MAP-Kinase cascade → removes Rb
Removal of Rb activates allows gene expression → protein synthesis can continue
, p53 :
If cellular damage occurs, p53 arrests
the cell cycle until the damage is
repaired.
If damage cannot be repaired,
apoptosis occurs.
Apoptosis
Programmed cell death
Based on caspase cascade:
Pro-caspases cleaved into caspases, activating caspase 3
Caspase 3 causes activation of cascade of caspase proteins
Cleaves various integral proteins, degrading cellular components (e.g. nucleus,
organelles, cytoskeleton)
Cell loses structure, resulting in blebs, which break off, undergo phagocytosis
Intrinsic/mitochondrial pathway
Induced by stress (e.g. radiation)
Process :
Intracellular proteins BAX, BAK pierce mitochondrial membrane
This alow s SMACS, cytochrome C to flow out of mitochondria
SMACS binds to proteins that otherwise inhibit apoptosis
Cytochrome C binds to ATP, APAF-1, forming apoptosome
Pro-caspase 9 cleaves into caspase 9, activating caspase 3
Extrinsic/death receptor pathway
Process :
External cell initiates apoptosis by releasing various signaling proteins
Signaling proteins bind to death receptors on cell membrane
Cytosolic end of protein dives deep into cell (AKA death domain)
Death domain changes shape, binds various proteins to form internal signalling complex
Pro-caspase 8 cleaves into caspase 8, activating caspase 3
Long notes
, #Genetics
Q. Describe the Cell Cycle. Write in detail about the Apoptosis and its role in
health and diseases.
Cell cycle is the series of growth and development steps in a cell separated by gap phases.
Total duration of cell cycle ranges from 12 to 24 hrs.
Two phases -
lnterphase: preparatory phase; cell performs basic functions, replicates DNA
Takes b/w 18-20hrs
Mitosis: cellular division
Takes about 2hrs
GO(G-ZERO) PHASE
Cells function but not dividing/preparing to divide
Considered out side cell cycle
INTERPHASE
Three sub phases: G1,S, G2 phases :
Gap/Growth 1 (Gl) phase
Longest phase
Cell grows while organelles function as usual
Terminates with G1 checkpoint
Cells with damaged DNA G0 / apoptosis
Lasts upto 10hrs
Synthesis (S) phase
DNA replicated (identical chromatids created)
Last about 5-6hrs
Gap/Growth 2 (G2) phase
Organelles duplicated
Terminates with G2 checkpoint
Last about 3-4hrs
M PHASE (MITOSIS & CYTOKINESIS)
Cell divides into two daughter cells
Prophase – nuclear membrane breaks down
Prometaphase – replicated chromosomes are lined up
, Metaphase – chromosomes separated into 2 sister chromatids
Anaphase – chromatids arrive at ends of cell, decondense & form
separate nuclear membranes
Telophase – Plasma membrane pinches cell into 2
(G0 Phase = Some cells (neurons) that don't divide, just stop at G0 )
In cytokinesis, the contractile ring in the cytoplasm of the cell pinches the
mother cell in two, producing two new daughter cells.
Daughter cells may immediately undergo many rounds of cell cycle or remain
dormant till further signal for division.
The Cell-Cycle Control System / Checkpoints :
- A complex network of regulatory proteins that ensures a cell replicates properly
- The cell checks that all critical earlier events have occurred:
Eg: DNAreplication
Eg: Segregationofduplicatedchromosomes
- Responds to various signals from outside & inside the cell
- Critical to regulation of cell numbers
- Malfunction can lead to cancer (Abnormal number of chromosomes/Mutated DNA)
- Can stop the cycle using molecular 'brakes' at 2 important checkpoints
,G1 Checkpoint: DNA damage prevents S-Phase Entry:
- Ensures environment is favourable for cell proliferation
- Ensures DNA is intact before committing it to replication (S-Phase)
- S-CdK :
Damaged DNA causes expression of a Cdk Inhibitor Protein that inactivates the S-Cdk
S-Cdk is necessary for DNA replication in S-Phase
Therefore, inactivation of S-Cdk arrests the cell cycle in G1 phase
G2 Checkpoint: DNA damage prevents M-Phase Entry
- Ensures that cells don't enter mitosis until DNA replication is completed correctly
- M-Cdk:
Similar function to S-Cd in the G1 Checkpoint
S-Cdk is inactivated by phosphorylation & activated by dephosphorylation
If DNA is good, Phosphatase Cdc25 removes the inhibitory phosphor, instantly
activating the M-Cdk
If DNA is bad, phosphatase Cdc25 is inactive, & therefore so is M-Cdk
- Active M-Cdk further activates phosphatase Cdc25 & also stops the Cdk-inhibitory
kinase from adding the inhibitory phosphor →→ triggers MITOSIS
The Spindle Checkpoint
The M checkpoint is also known as the spindle checkpoint: here, the cell examines
whether all the sister chromatids are correctly attached to the spindle microtubules at
metaphase plate.
Cdc6:
Cdc6 is a regulatory protein that binds to ORC's (Origin Recognition Complexes) on DNA
Prevents DNA Replication until G1 checkpoint is satisfied
Activated S-Cdk removes Cdc6 via phosphorylation → allows DNA replication to continue
Rb-protein (Gene Regulatory Protein-B):
Rb-Protein is another regulatory protein that prevents gene transcription of S-Phase
proteins
Requires the presence of external growth-factors → intracellular cascade
Enzyme-linked receptor → Ras activated
Ras → MAP-Kinase cascade → removes Rb
Removal of Rb activates allows gene expression → protein synthesis can continue
, p53 :
If cellular damage occurs, p53 arrests
the cell cycle until the damage is
repaired.
If damage cannot be repaired,
apoptosis occurs.
Apoptosis
Programmed cell death
Based on caspase cascade:
Pro-caspases cleaved into caspases, activating caspase 3
Caspase 3 causes activation of cascade of caspase proteins
Cleaves various integral proteins, degrading cellular components (e.g. nucleus,
organelles, cytoskeleton)
Cell loses structure, resulting in blebs, which break off, undergo phagocytosis
Intrinsic/mitochondrial pathway
Induced by stress (e.g. radiation)
Process :
Intracellular proteins BAX, BAK pierce mitochondrial membrane
This alow s SMACS, cytochrome C to flow out of mitochondria
SMACS binds to proteins that otherwise inhibit apoptosis
Cytochrome C binds to ATP, APAF-1, forming apoptosome
Pro-caspase 9 cleaves into caspase 9, activating caspase 3
Extrinsic/death receptor pathway
Process :
External cell initiates apoptosis by releasing various signaling proteins
Signaling proteins bind to death receptors on cell membrane
Cytosolic end of protein dives deep into cell (AKA death domain)
Death domain changes shape, binds various proteins to form internal signalling complex
Pro-caspase 8 cleaves into caspase 8, activating caspase 3
