chapter 15: cell cycle control Flashcards
G2 checkpoint (how to pass)
pass checkpoint if
1. chromosomes have replicated successfully
2. DNA is undamaged
3. activated MPF is present
metaphase checkpoint (how to pass)
pass checkpoint if
1. chromosomes have attached to spindle apparatus
2. chromosomes have properly separated and MPF is absent
G0 exit
differentiated cells exit the cell cycle and do specific functions in the tissue they reside
G1 checkpoint (how to pass)
pass checkpoint if
1. cell size is adequate
2. nutrients are sufficient
3. social signals are present (do we need a new cell?)
4. DNA is undamaged (most important)
G1 checkpoint (general info)
- most important in establishing whether a cell will continue or exit to G0
- p53 protein activates genes that either stop the cell cycle until DNA damage can be repaired
what promotes division?
growth factors
when is cdk active?
not until cyclins bind
what is needed to pass G1 checkpoint?
cyclin and E2F proteins
steps to pass G1 checkpoint
- growth factors arrive from other cells
- cells produce cyclin and e2f
- cyclin binds to cdk
- cdk phosphorylates Rb after inactivating phosphate is removed
- phosphorylated Rb releases e2f
- e2f triggers production of s-phase proteins
E2F protein
- binds to Rb which inactivates the E2F
- activates formation of DNA poly, helicase, ligase, primase, ssbp
3 possible outcomes if DNA is damaged
- dna gets repaired
- senescense (stays in G1)
- cell death
p53 proteins
- signal to stop cell division if DNA damage is present
- creates cdk inhibitor
- prefer cell death over DNA repair
what is DNA damage caused by
mutagens: chemicals, UV radiation, x-rays, etc
nucleotide extension repair steps
- error detection
- DNA nicking
- nucleotide excision
- nucleotide placement
- nucleotide linkage
error detection (nucleotide extension repair)
a complex of proteins detects an irregularity in DNA structure
DNA nicking
an enzyme nicks DNA on both sides of the damage
nucleotide excision
a DNA helicase unwinds and removed the region with the undamaged bases
nucleotide placement
DNA polymerase fills in the gap in the 5’ to 3’ direction using the undamaged strand as a template
nucleotide linkage
DNA ligase links the newly synthesized DNA to the preexisting strand
uvrA
protein that recognizes DNA damage and signals to start repair mechanisms in e. coli
- cells cant survive without this
recA
protein that facilitates DNA repair in e. coli
telomeres
- must be long enough to pass checkpoint 1
- act as a buffer for chromosomes following DNA replication
- no genes in the telomere region
- solely to protect
problem with the lagging strand
DNA polymerase cannot replicate the ends of the lagging strand because there is no 3’-OH for covalent extension
Hayflick limit
average number of times a normal human cell population will divide before becoming senescent and dying
telomere shortening rate predicts?
species life span
telomerase
- enzyme containing an RNA primer and restores telomere length, maintaining the replicative capacity of cells
- telomerase activity extinguished during embryonic differentiation in majority of cells
- some stem cells still have
DNA polymerase (G2 checkpoint)
- can recognize a mismatch, back up, remove nucleotide, and continue synthesis
- 99% of mismatches are recognized and removed
- mismatches are recognized by abnormal hydrogen bonding
MPF
- m phase promoting factor
- cyclin-cdk complex that initiates mitosis
- activity increases as cell makes more cyclin
only phase of mitosis that gets checked
metaphase checkpoint: are the spindles attached correctly
mutation that is often a predictor of cancer
BRCA1
how does BRCA1 mutation predict cancer
the enzyme made from BRCA1 gene fixes DNA damage, so when it mutates, there is a higher chance of mutations occurring and not being fixed
- genome instability = mutations accumulate
quinolones
- a cancer treatment
- inhibit topoisomerase to disrupt DNA synthesis
- if no new DNA can be synthesized, cells will stop dividing
- will not make it past the G2 checkpoint
taxol
- a cancer treatment
- destabilizes microtubules to stop cell division during M phase
stathmin
- cancer treatment
- promotes depolymerization and prevents polymerization
- microtubule regulator
