Cell Cycle Dysregulation Flashcards
the cell cycle clock operates in the
cells’ nucleus
the cell cycle clock processes..
incoming signals both from inside and outside the cell
the cell cycle clock decides on
-entering active cell cycle
-retreating into nonproliferating state
what are known as the cell cycle regulators
promoting & inhibiting factors
what is known as the S phase promoting factor
cyclin A/ CDK2
what is known as the maturation promoting factor
cyclin B/ CDC25B
which inhibitory factor inhibits CDK4/6
P16INK4
which inhibitory factor…
makes sure damaged DNA is NOT copied
blocks advancement into R point
stimulates formation of cyclin D/ CDK4,6 complex
is found in high conc. when the cell is in G0
P27KIP1
Growth factors stimulate the cell to produce _____ which bind _____.
cyclins
Cdks
what controls the different stages of the cell cycle
different cyclin/Cdk complexes
cyclin B forms complexes that…
allow entrance into M phase
cyclin E increases..
after passing R point
cyclin A increases…
with cells entrance into S phase
what are the 4 different checkpoints for DNA damage
- spindle assembly checkpoint
- G1 checkpoint
- S checkpoint
- G2 checkpoint
the spindle assembly checkpoint checks for…
- chromosome attachment to spindle
- chromosome alignment
the G1 checkpoint checks for…
- cell size
- nutrients
- GF
- DNA damage
the S checkpoint checks for…
- only 1 DNA replication
- DNA damage
the G2 checkpoint checks for…
- cell size
- DNA replication
- DNA damage
the spindle assembly checkpoint occurs during the
M phase
what results from any DNA damage that is detected by cell cycle checkpoints?
transient cycle arrest
what are the steps needed to surpass the restriction point of the cell cycle?
- GF bind to receptor producing active Cdk-cyclin
- Cdk-cyclin adds phosphate group to Rb protein
- Rb can NOT exert inhibitory influence -> E2F is released
- cells move into S phase (transcription)
what licensing factor can only bind in G1
MCM helicase
what are 3 consequences of losing control of cell cycle checkpoints?
- rereplication of previously replicated DNA
- cells gain or lose chromosomes
- DNA damage goes undetected
the loss of what checkpoint gene leads to the re-replication of DNA?
Rad17
the absence of what protein causes improper alignment during metaphase
Bub1
- normally prevents separation of chromosomes if not aligned properly
cells that lack _____ have fragile sites in the chromosomes
ATR protein kinase
what is the function of ATR protein kinase?
stopping DNA replication until replication forks are repaired
explain the steps in cdk/cyclin regulation
- mitotic Cdk and mitotic cyclin bind forming an inactive complex
- inhibiting kinases attach 2 inhibitory phosphate groups to the Cdk molecule
- activating kinases add an activating phosphate group
- phosphatase removes the inhibiting phosphate groups activating the Cdk-cyclin complex
Cdk/cyclin regulation is through
double phosphorylation by kinases and dephosphorylation by phosphatases
wild type p53…
suppresses cell proliferation
what causes p53 to become growth promoting
a point mutation in the reading frame
sensor proteins recognize damaged DNA and activate…
ATM
what role of p53 in response to DNA damage leads to cell cycle arrest
p21 inhibits Cdk-cyclin complex leading to cell cycle arrest
during the role of p53 in response to DNA damage why can Cdk-cyclin not activate mitosis
b/c Cdk-cyclin can NOT phosphorylate Rb protein
what role of p53 in response to DNA damage leads to apoptosis
puma is activated binding to Bcl2 relieving its inhibition on proapoptotic Bax
list 6 factors that cause p53 levels to rise
- lack of nucleotides
- UV radiation
- ionizing radiation
- oncogene signaling
- hypoxia
- blockage of transcription
after p52 levels rise p53 undergoes..
post-translational modifications
post-translational modifications in p53 lead to what 4 responses
- cell cycle arrest
- DNA repair
- angiogenesis blocked
- apoptosis
what is the most commonly mutated gene in human cancers?
p53
which mutations in mouse germ line alleles resulted in succumbing to malignancies by day 250?
those missing both alleles (homozygotes)
what does APC stand for
anaphase promoting complex
APC’s function
triggers anaphase
how does APC trigger anaphase
by activating enzymes that degrade cohesins
what checkpoint delays anaphase until chromosomes have been attached to the spindles?
spindle checkpoint
what is the “wait” signal that chromosomes send when they’re not properly attached to the spindles
Mad-Bub
how does Mad-Bub function as a ‘wait’ signal?
by inhibiting Cdc20 which is need for chromosome separation
function of Cdc20
activates separase enzyme
