cell cycle regulation Flashcards
what are the stages of the cell cycle?
G1, G0, S, G2, M (includes mitosis and cytokinesis)
what is the key event in mitosis?
the metaphase to anaphase transition
combining a cell in S phase with one in G1 phase results in?
both cells pass S and replicate DNA
combining a cell in S phase with one in the G2 phase results in?
only the S phase nucleus replicating DNA because the G2 nucleus cannot move backwards back into S
what are the conditions that must be respected when working with yeast
the effect of the mutation is viable and can be seen only is specific conditions, such as single-gene temperature sensitive mutants that stop dividing at restrictive temps
what is the advantage of xenopus as a study?
all embryos are synchronized, and cleavage occurs even without DNA replication
what is the domino hypothesis?
the events of the cell cycle must be completed for the next phase to begin
what is the clock/timer hypothesis?
that events of the cell cycle must be completed in a certain timeframe after which the cell even if it hasn’t completed that phase it will enter the next phase
explain how the cell cycle is controlled
by both the Clock (biochemical switches turn on specific events in a certain order and at a certain time) and the Domino (internal and external factors modulate the clock if the phase hasn’t been completed)
what are the components of the MPF?
a kinase and a cyclin
when are CDK’s active?
only when they are bound to the regulatory protein cyclin (this is always present in the cell at varying concentrations)
CDK and cyclin work together as?
a kinase
when is cyclin at its highest concentration?
it starts to accumulate at interphase (G1,S,G2) and peaks at mitosis and then falls
when is cyclin D and E present
at G1
when is cyclin A present?
at S and G2 and some of M
when is cyclin B present
at the first half of mitosis
how is cyclin-CDK activity regulated?
by degradation of cyclin’s by proteolysis, by modulation by de/phosphorylation. CDK inhibitors
what is responsible for the oscillation of the cyclin levels?
the regulated proteasome-mediated degradation, the ubiquitin chain can degrade a cyclin
what is the function of Wee1 kinase?
inhibition of mitotic CDK-cyclin complex
what is the purpose of Cdc25 phosphatase?
activation of mitotic CDK-cyclin complex
what are the 2 inhibitor families?
Cip/Kip (p21) which act in G1 and S phase, and Ink4 which is selective inhibition of cdk D cyclin complexes acting in G1
inhibition of CDK do what?
they block entry to S phase
inhibition of cyclin degradation results in?
delays exit from mitosis (it is and inhibition of APC activation)
what does inhibition of activating phosphatase do?
blocks the entry to mitosis
name the 3 check points for the cell cycle
the start or restriction checkpoint (G1/S), the G2/M checkpoint, the metaphase/anaphase checkpoint
what are the conditions checked at the G1/S point
If the environment is favorable. There is nutrient availability, there are growth factors/mitogens, cell size is fine, DNA integrity, note that CDK are inactive in G1
what are the conditions looked for at G2/M point
is all DNA replicated, is all DNA damage repaired
what at the conditions of the Metaphase/anaphase point
are all the chromosomes properly attached to the mitotic spindle
progress past the G1/S checkpoint depends on Rb. How?
one of the substrates of G1 cyclin-cdk complex is Rb protein, normally rb inhibits entrance into S , phosphorylation inactivates Rb so that the cells can enter S
what is the role of p53
if DNA is damages then the p53 protein blocks the cell cycle and it is a transcription factor which promotes transcription of CDK inhibitor (p21)
explain the control of the G2/M point
the mitotic-cdk complex are kept inactive by phosphorylation done by Wee1 kinase, when conditions are ok the mitotic cdk complex id dephosphorylated, the cell can now enter mitosis
how does mitotic cyclin-cdk complex induce entry into mitosis
by inducing the breakdown of the nuclear envelope, by inducing chromosome condensation, by inducing mitotic spindle assembly
what is the APC
the activation of the anaphase promoting complex is a needed event in order to pass from metaphase to anaphase. APC is a ubiquitin ligase so it marks proteins for proteasome mediated degrading, its targets are securing and cyclin.
APC activates separase
APC kept inactive by spindle checkpoint proteins
- APC is activated by mytotic cyclin/Cdk complex
- APC send securin to degradation
- Separase is active and remove cohesins holding together sister chromatids
what are the best organisms to study the cell cycle
budding yeast and fission yeast (S. cerevisiae, S.Pombe), sea urchins, cams, frogs, mammalian cell cultures
