Cell Cycle & Cancer Flashcards
What is the primary role of the G1 phase? What other functions occur?
Primary role: Sense DNA damage
Other functions: synthesize proteins necessary for DNA replication, increases in cell size
What is the primary role of the S phase in the cell cycle? What is doubled?
Primary role: DNA synthesis
Number of genetic material is doubled, there are now 46 chromosomes
What is the primary role of G2? Other functions?
Primary role: Synthesize things needed for mitosis for cell survival
increased cell growth
What is the function of mitosis and the phases of mitosis?
Function of mitosis: DNA condensation to chromatin
Prophase: DNA condenses into sister chromatid
Metaphase: DNA aligns in the center to prepare for separation
Anaphase: DNA begins to separate and move to opposite poles
Telophase: DNA begin dividing into 2
Function of G0? What cells go to G0?
Function of G0 is to sequester cells not ready for cell division. Either due to cell damage or division of the cell is not needed in the body at that time. Cells are arrested either until they are given the sequence to initiate move into G1 or are too damaged to be repaired and are marked for apoptosis
What are the two mechanisms for programmed cell death and their pathways?
Intrinsic cell death (mitochondrial)
- -Propoptic: BAK, BAX. Create pores in the mitochondrial membrane that release cytochrome C and induce apoptosis
- -Antipropotic: Bcl-2, Bcl-xL. Make the mitochondrial membrane impermeable so that cytochrome C cannot be released and inhibits apoptosis.
Extrinsic cell death
- -Ligand mediated: FasL/Fas or TNF-alpha/TNF bind together and initiate the release of initiator caspases that then signal the release of the caspases that trigger apoptosis
- -Cytotoxic T cell: GRANENZYME perforates cell membrane releasing PERFORIN which activates caspases that trigger apoptosis
Differences between apoptosis and necrosis
Apoptosis: programmed/regulated, non-inflammatory, cell membrane remains intact
Necrosis: not planned, always pathological, always inflammatory, cell membrane disrupted, macrophage digestion
Which part of the cell cycle does each cyclin regulate and with what respective cyclin-dependent kinase
Cyclin D/CDK4/CDK6: G1 –> S
Cyclin E/CDK2: G1 –> S (helps to finish transition)
Cyclin A/CDK1/CDK2: S & G2 (only cyclin that is responsible for 2 phases)
Cyclin B/CDK1: Mitosis
What is the function of cyclins? What is the function of cyclin-dependent kinases?
Cyclin by itself is unstable. CDKs stabilize cyclin when they bind. The only role of cyclin is to move cells further in the cell cycle. CDKs are indirect regulators of cyclin
How do cyclins regulate themselves?
- Cyclin-inhibition kinases: inhibit the activation of CDK/cyclin complexes downstream
- The structure of cyclin is unstable with a short half life and will naturally ensure that expression stops
What role does the tumor suppressor Rb play in regulation of cell cycle progression and by what mechanism and which part of the cell cycle?
Rb is an indirect inhibitor of the cell cycle. E2F is a protein that must be expressed in order for S proteins to be expressed and cell cycle progression to continue. When cyclin D is activated and binds to CDK4, the cyclin D/CDK4 complex goes to phosphorylate the Rb/E2F complex. The phosphorylation decreases affinity between Rb and E2F so that as long as Rb is continually phosphorylated then E2F will be expressed and the cell cycle will progress past the G1/S checkpoint
What role does p53 play in cell cycle progression. Which part of cell cycle? By what mechanism?
P53 inhibits progression at the G1/S checkpoint. p53 binds to damaged DNA and makes p21. This p21 acts as an inhibitor and binds to cyclin E/CDK2 to inhibit cell cycle progression. DNA is given a chance to repair itself before it goes into the cell cycle. If p53 is expressed for too long, the cell is marked for apoptosis because the DNA damage is too much to repair
Describe the function of each cell cycle checkpoint
G1/S: MAJOR checkpoint. Ensures that there is no damaged DNA
G2/M: Ensures that all the DNA made it to decrease the risk of aneuploidy
Mitosis metaphase: Ensures that the sister chromatids are aligned so that they split evenly
What are the mechanisms of cancer pharmacotherapy?
- Cytotoxic chemotherapy: CELLULAR POISON to stop proliferation of abnormal cells
- Molecularly targeted therapy: targets specific receptors/pathways
- Immunotherapy: aids the immune system in attacking
- Endocrine therapy: treats cancers that have specific hormone receptors by blocking/modifying the hormone
S phase cytotoxic drugs
Antimetabolites (Azathioprine, methotrexate)
