Exam 4: 503 - Roberts - Cell Cycle And Apoptosis

Front 1

Be able to describe the stages of the cell cycle (M, G1, S, G2).

Back 1

• M = actual cell division, a short phase.
• G1 = cell growth, normal functioning (G0 in a non-dividing cell type).
• S = duplication of DNA
• G2 = between DNA duplication and actual cell division (between S and M phases).
• INTERPHASE includes G1, S, and G2!

Front 2

Know what cyclins and CDKs are.

Back 2

• Cyclins – Are regulatory subunits that convey target specificity, in the protein kinase machinery of the cell cycle control system.
• CDKs – The catalytic subunit, that are inactive without cyclin, in the protein kinase machinery of the cell cycle control system.

Front 3

Know how cyclins activate CDKs. Understand that cyclins undergo cycles of synthesis and degradation (role of ubiquitin).

Back 3

1) Binding to inactive CDK to make it partially active (removes protein-blocking slab)
2) Phosphorylating CDK via CDK-activating kinase to make CDK fully active.

Front 4

Understand that cyclins undergo cycles of synthesis and degradation (role of ubiquitin).

Back 4

Cyclin now gets degraded via ubiquitination. Ubiquitination is also degrades MCDK and SCDK.

Front 5

Know the 4 cyclins (D, E, A, B), and at what step in the cell cycle they are utilized. Know the terms G1-CDK etc. (see slide 12)

Back 5

• G1-Cdk – The complex formed by Cyclin D-Cdk4, Cdk6 association that moves cell into passage through the G1 phase.
• G1/S-Cdk – The complex formed by Cyclin E-Cdk2 association that commits the cell to DNA replication.
• S-Cdk – The complex formed by Cyclin A-Cdk2 association that is required for the cell to proceed through the S phase.
• M-Cdk – The complex formed by cyclin B-Cdk1 association that promotes mitosis.

Front 6

Understand the concept of checkpoints and where the three main checkpoints occur.

Back 6

I. G1 – Is the cell big enough? Is the DNA correct? Environment stable? Occurs before S phase (synthesis phase).
II. G2 – Is all the DNA replicated? Any errors? Is cell big enough? Stockpile of inactive M-Cdk exists by the end of G2; if things are okay, M-Cdk gets activated to allow the cell to progress through the G2 checkpoint. Occurs before M phase (mitotic phase).
III. M- Are the chromosomes aligned? Are they attached to the spindle fibers?

Front 7

Know that the main DNA damage checkpoints occur in
a) late G1 and b) late G2

Back 7

a) Preventing entry into S-phase.
b) Preventing entry into mitosis.

Front 8

Understand the importance of Rb for transitioning into S-phase.

Back 8

- Retinoblastoma protein binds to E2F protein to sequester it away (keeps it inactive).
- Active G1-Cdk comes in to phosphorylate Rb to make it inactive.
- Rb disassociates from E2F protein to cause E2F to become active.
- E2F can now progress through S-phase (start transcription).

Front 9

Understand what occurs in terminally differentiated cells and that they remain in G1/G0 phase.

Back 9

These cells’ (which include neurons and skeletal muscle cells) cell cycle control system is completely dismantled. They don’t replicate, they just stay in G1 phase forever.

Front 10

Understand why apoptosis is useful (development, in adult tissue). Appreciate that apoptotic cells are engulfed by phagocytic cells and do not elicit an inflammatory response.

Back 10

See Notes

Front 11

Know the main steps of apoptosis.

Back 11

I. Cell Shrinks
II. Cytoskeleton collapses
III. Nucleus condenses
IV. DNA fragmentation
V. Membrane blebbing (bubbling)
VI. Cell surface changes (phosphatidylserine)
VII. Cell fragments are engulfed by phagocytic cells

Front 12

Understand the role of caspases and how they act.

Back 12

- Are part of a family of proteases with a cysteine at the active site that cleave target proteins at specific aspartic acid residues. Caspases also activate other caspases.
- Acts through either:
1) Extrinsic pathway – Death receptors become triggered by a signal and activate the caspase cascade.
2) Intrinsic pathway – Due to too much DNA damage, mitochondria release cytochrome c, which interacts with an adaptor and together they activate the caspase cascade.

Front 13

Know that apoptosis can be triggered by outside (death receptors) or inside (cytochrome c release from mitochondria) signals.

Back 13

See Notes

Front 14

Know the overall importance of apoptosis for diseases.

Back 14

See Notes