Mol Lecture #19 Flashcards
Anaphase
- Separase (protein) releases the sister chromatids by cleaving cohesins (at this point, they are now called daughter chromosomes)
- Daughter chromosomes move along the kinetochore microtubules
- Non-kinetochore microtubules slide in opposing directions to push the two ends of the cells father apart.
Telophase
- Putting the cells back together in an interphase state.
- Undoing the events of prophase and Prometaphase
→ chromosomes uncondensed
→ reform the nuclear envelope
→ disassemble the mitotic spindle
Cytokinesis
- Microfilament structure pinches daughter cells apart along the former spindle midpoint.
- Make sure that everything is equally distributed
Getting the DNA to each side is the most important aspect along the lines of equally distributing.
Regulation of the Cell Cycle: What does it entail? What could happen?
- Cell division is closely tied to the need of the organism
- Constantly replacing things (ex. Lining of the intestinal tract)
- Ex. Increase in the amount of the production of red blood cells
- When this doesn’t go correctly it could lead to cancer or inflammation
G1phase + Every other part of the cycle
- Do we want to divide or not
- Have we done the last step correctly
Cell Cycle checkpoints
- Multiple points during which the cell takes stock of itself and its surroundings to determine if the cell cycle should proceed. Think of these points where ‘brakes’ might be applied. ‘Passing’ the checkpoint allows the next phase to proceed.
- G1/S checkpoint
- G2/M checkpoint
- Mitotic Spindle Checkpoint
G1/S checkpoint
- Check to see if there’s anything wrong with the cell. See if the organism wants new cells (needs of the organism)
G2/M checkpoint
- Check to see if the DNA was copied correctly. Check to see if there’s anything else wrong with the cell that would prevent moving forward.
Mitotic Spindle Checkpoint
- make sure that the chromosomes are aligned correctly (metaphase to anaphase checkpoint)
Molecular regulation of the cell cycle: Involves 2 components
Cyclins and CDKs
Cyclin-dependent kinase (CdK’s):
- enzymes that activate downstream targets by phosphorylating them. (covalently add a phosphate group onto the protein, which activates the downstream proteins (the proteins breaking down the nuclear envelope, etc.))
→ CdK’s change activity during the cell cycle
Cyclin:
-proteins that change in amount during the cell cycle. Control the activity of the CdKs by interacting with them
G1/S cyclin:
- binds to CdK2 during G1 (Target: DNA polymerase- phosphorylates DNA to prepare it for DNA replication)
S cyclin:
- binds CdK2 during S-phase to initiate DNA replication
M cyclin:
- binds to CdK1 in G2 to stimulate mitosis. (phosphorylates nuclear lamins)
Mechanisms of Regulation
- M cyclin will take the whole gap phase to produce an effect.
Cyclins and CdKs
- Timeline of cyclin production
- The dramatic drops in the amount of cyclins are also regulated
- The cyclins are changing in amount of cell cycles, while CdKs are changing in amount of activity.
Big picture of Cyclins and CdKs
Big picture: Gene regulation mirroring (transcriptional level, post-transcriptional level, and protein expression…)
Cell Cycle is coordinated with activities of the organism
- Positively and negatively influence the cell cycle
- Stimulation of cell division by a growth factor
- Inhibition
Growth factor
- growth factors enact signal transduction pathways to tell a cell to divide
- involves a protein
Inhibition Factor
- growth inhibiting factors stop the cell from dividing, it causes the increase in gene expression of factors that inhibit cell division
→ one of those factors is contact inhibition: when cells touch, it often inhibits cell cycle progression - involves a protein
Cancer
- A collection of multiple diseases with similar genetic causes and phenotypic changes in cells affecting multiple tissues
- Cancers are genetic diseases (genetic basis) resulting in the loss of regulation of normal cell biology to give rise to abnormal cells
Two main characteristics of cancer cells:
1) Unregulated cell division, no longer tied to the needs of the organism
2) Cancer cells invade and colonize other tissues
Multistep progression of cancer
- Multistep process that requires multiple genetic alterations. These genetic changes impact cell cycle controls and the cell’s ability to be regulated by the organism’s needs.
Multistep progression of cancer (ex. Colon Cancer)
- You need multiple changes from a normal colon cell to a cancerous one.
- Two base changes and the additional changes in the behavior of the cells along with a loss of a gene.
- Variability in mutations acquired (tumor growth, etc.)
Mutations in Cancer: 2 types of mutations
- Gain of function mutations in proto-oncogenes
- Loss of function mutations
Gain of function
Genes that usually stimulate the cell cycle- gas pedal of the cell cycle- to make them oncogenes (turning those genes on)
Loss of function mutation
- Tumor suppressors (genes that generally inhibit the cell cycle- brake pedal) (turning these off)
Mutations affecting cell cycle in cancer
- Genes that affect G1 cyclin might be changed
- Telomerase- can be considered a proto-oncogene
