Cancer Biology Flashcards
How many chromosomes need to be mutated to have activation of oncogenes?
One of the two chromosomes in a pair
How many chromosomes need to be mutated to have inactivation of Tumor Supressor Gene?
Both chromosomes in the pair
What are the 2 phases of the cell cycle?
- Interphase
- Mitosis
Interphase
- longest part
- state of preparation
- cell performs basic functions
- grows and replicates DNA
What are the 3 sub-phases of Interphase?
(1) G1
(2) S
(3) G2
G1 Phase
- longest sub-phase
- cell grows
- organelles perform normal functions like synthesis of proteins and energy production
- chromosomes are made-up of a single chromatid
- control point at G1 called G1 checkpoint
G1/S Checkpoint
- RESTRICTION POINT
- checks for damaged DNA
- mediated by cyclin E/CDK2 complex and Rb protein and E2F
- when cyclin E/CDK2 complex forms, it phosphorylates Rb which releases E2F; E2F then binds to promoter region and upregulates proteins required for DNA replication (i.e. DNA polymerase)
S Phase
- DNA is replicated
- each daughter cell receives identical copies of genetic material
- number of chromosomes does not change – still 46 chromosomes
- amount of DNA doubles
- 2 identical chromatids makeup chromosome
G2 Phase
- cell must duplicate organelles
- G2 checkpoint
Mitosis
- occurs after/during G2 phase
- cell divides into two daughter cells
- steps:
(1) Prophase: nuclear membrane disintegrates, chromosomes condense, centrosomes migrate to opposite ends of cell
(2) Metaphase: chromosomes move toward center of cell on line called metaphase plate, centrosome sends out spindle fibers to attach to centromere of each chromosome
(3) Anaphase: centrosomes pull sister chromatids apart
(4) Telophase: nuclear membrane forms around each new set of 46 single chromatid chromosomes
(5) Cytokinesis: pinching of cell membrane until daughter cells separate
G0 Phase
- cells can enter here after G2/M
- non-dividing phase (not actively dividing or preparing to divide)
- phase outside the cell cycle
- Examples: Hepatocytes, Neurons
Proto-Oncogenes
stimulate cell proliferation
Cyclin bound to CDK ___ the progression of the cell cycle/proliferation
activates
Rb bound to E2F __ the progression of the cell cycle/proliferation
inhibits
Rb bound to E2F __ the progression of the cell cycle/proliferation
inhibits
ATM
- gene that produces different types of proteins/enzymes that sense DNA damage
- gene responsible for initiating proofreading of DNA
P53
- most important tumor suppressor gene
- gene that is activated when ATM derived proteins/enzymes sense damage/mistake in DNA; responds by inducing P21 which is the protein that inhibits formation of all cyclin/CDK complexes (cell unable to move thru cell cycle b/c of this)
- ensures only cells free of DNA errors can undergo cell division
- if cell contains DNA errors then P53 will arrest cell division until repair is made or it will trigger apoptosis of cell
- loss of P53 leads to accumulation of DNA mutations and eventually cancer
What cell phase in the cell cycle is Cyclin E at its highest concentration?
Checkpoint of G1/S
What cell phase in the cell cycle is Cyclin A at its highest concentration?
G2 Phase
What cell phase in the cell cycle is Cyclin B at its highest concentration?
G2/Mitosis
Rb
- present at restriction point in G1
- function: prevent excessive cell division by inhibiting cell cycle progression
- normally bound to transcription factor E2F (inactivates it) when cell cycle functioning normally/not actively dividing
- inactivated when phosphorylated by Cyclin E/Cdk2 complex
- if mutated, unable to bind E2F which leads to continuous activation of proteins required for DNA replication/cell division