Chapter 18 Flashcards
mitosis divides ____ while ____ divides cytoplasm
mitosis divides chromosomes
cytokinesis divides cytoplasm
to reproduce all cells go thru a series of events called ___ ____
what does it do and what is produced?
cell cycle
cells grow, duplicate, segregate and it produces 2 genetically identical daughter cells
is the length of the cell cycle the same for all cells?
NO, it varies
mostly comes from variation in G1 phase
what are the interphase sub-phases and what do each do
G1 = day to day activities/ growth
S phase =synthesis / DNA replication
G2 = prepares for division
what makes up the M phase
mitosis then cytokinesis
mitosis = PMAT
describe G0
happens in G1 = some cells will exit the cell cycle, temporarily or permanently
permanently - terminally differentiated/highly specialized cells that do not divide
temporarily - some cells don’t normally divide but can when given a stimulus
what is the cell cycle control system
3 main checkpoints
- before entering S phase (G1/S-Cdk /Rb, p53)
- before entering M phase (M-Cdk/ Cdc25)
- in anaphase (APC)
what are the 2 most important protein families in cell cycle control and describe
- Cyclins
-regulatory proteins that bind to Cdks
-no enzymatic activity
- !concentrations! fluctuate in cyclic manner - Cyclin-dependent protein kinases (Cdks)
-cyclins bind to them
-enzymatic activity by cyclin binding
-activated by phosphorylation/dephosphorylation
- concentrations remain same !activity! fluctuates
- are kinases so phosphorylate other proteins
the 4 main cyclin-Cdk complexes
G1-Cdk
G1-S-Cdk (start)
S-Cdk (entry into S)
M-Cdk (entry into M)
when will Cdk activity be the highest ?
when cyclins levels are high
what does an increase in cyclin vs a decrease mean
increase = increased transcription of cyclin genes
decreased = targeted destruction (ubiquitin)
Cdks are ____ when the cyclins are degraded
inactivated
activation of Cdks depends on …. (3)
- phosphorylation of Cdk
- binding of Cdk to cyclin partner to produce cyclin-Cdk complex
- activation of cyclin-Cdk complex by dephosphorylation (one P remains)
activity of cyclin-Cdk complexes can be decreased by …. (3)
- degradation of cyclins
- inhibitory proteins
- inhibitors
describe Wee1
a kinase
= inactivates cyclin-Cdk by ADDING 2 inhibitory phosphates
describe Cdc25
a phosphatase = activates cyclin-Cdk by REMOVING the 2 inhibitory phosphates
what are the 2 inhibitors in cell cycle control
can regulate cyclin-Cdk activity
-p27 and p21
=physically blocks it from interacting with proteins / cyclin-Cdk cant phosphorylate
ex. p27 prevents entry into S phase
Cyclin-Cdk complexes are responsible for ____
phosphorylating target proteins
cyclin-Cdk activity is regulated by _____ & _____
phosphorylation and dephosphorylation
describe G1
day to day activities
-can go into S phase, pause in G1 or enter G0
-at start of G1 all Cdks are INACTIVATED
describe Rb and Mitogens in G1
Rb (retinoblastoma protein) = inhibits TFs (E2Fs)
- Mitogen once bound to cell surface receptors turns on G1/S-Cdk via intracellular signaling, which phosphorylates Rb, inactivating it
- now that Rb is inactive transcription can occur (stimulate cell proliferation)and cell can enter S phase
*without mitogens Rb inhibits transcription / stays in G1 (halting cell division)
what two things can halt progression into S phase
Rb and p53&p21
DNA damage results in ___ and describe what is produces
activation of p53 protein (TF)
p21 is produced
-p21 = Cdk inhibitor that binds to G1/S-Cdk and S-Cdk and INACTIVATES them which causes cell to pause in G1 and repair
*can also halt G2->M
what does S-Cdk do
S-Cdk initiates DNA replication and prevents re-replication
describe S phase
G1
1. ORC recruits Cdc6
2. Cdc6 rises early in G1 and helps load helicase at Ori
3. S-Cdk is assembled and activated at end of G1
S PHASE
4. S-Cdk activates helicase and other replication enzymes thru phosphorylation
5. S-Cdk “pulls the trigger” that initiates DNA synthesis
6. S-Cdk blocks re-replication by inactivating Cdc6 (marks for degradation)
describe G2 if DNA is not replicated correctly phase
if DNA is not replicated correctly or cell too big must delay entry into M phase
so inhibit Cdc25
-Cdc25 is inactivated so that M-Cdk remains inactive and cell cycle halts in G2 phase until ready
how is M-Cdk activated
when Cdc25 removes the inhibitory phosphates
active M-Cdk acts via ___ ____ loop, activating more ____ which activates more ____
active M-Cdk acts via positive feedback loop, activating more Cdc25 which activates more M-Cdk
describe entry into M phase (2)
- active M-Cdk activates Cdc25 and shuts down Wee1 kinase
-inactive M-Cdk are stockpiled during G2 but are not activated till end of G2 and once activated they drive entry into M phase
what shifts a cell from G2 into Mitosis
massive increase in active M-Cdk
what are cohesin
large protein ring that wraps around two sister chromatids, holding them together so they wont separate until anaphase
what are condensins
bind to chromatin to help it coil into mitotic chromosomes
-M-Cdk phosphorylates them to activate them
-trigger compaction of chromatin into condensed mitotic chromosomes
what happens in prophase
chromosomes condense and move to opposite sides of nucleus / formation of mitotic spindle
-cohesins and condensins
M-Cdk phosphorylates NPCs and _____ triggering what
NPCs and nuclear lamins, triggering disassembly of nuclear lamina and leading to the breakdown of nuclear envelope
when is the nuclear envelope broken down and when is it reassembled
broken down - prophase (proteins phosphorylated)
reassembled - telophase (proteins dephosphorylated)
the cytoskeleton filaments that form the mitotic spindle are ___ and those involved in the contractile ring in cytokinesis are ____
microtubules and actin (microfilaments)
what is the mitotic spindle in and what is it
in mitosis = is microtubules and kinesin/dynein motor proteins that separate chromosomes
what is the contractile ring in and what is it
in cytokinesis = is made of actin filaments and myosin motor proteins which separates 2 daughter cells
steps of the centrosome cycle (3)
- centrosome is duplicated in S phase so that each centrosome can form one pole of the mitotic spindle
- happens in S phase to G2
- triggered by G1/S-Cdk and S-Cdk
what is an aster
short microtubules that extend out from the centrosome towards cortex
describe metaphase
-sister chromatids become attached to MT by their kinetochores
-chromosomes are moved and aligned in middle
-in middle, at metaphase plate, sister chromatids are constantly pulled on by MTs at each pole creating tension
does the + or - end of MT bind to kinetochore
+ end
what generates the tension in metaphase
kinetochore MTs from each pole will attach to opposing kinetochores on sister chromatids
describe what happens in anaphase (3) and what is it triggered by
-sudden synchronous splitting apart of centromeres
-separation of sister chromatids to form daughter chromosomes
-movement of daughter chromosomes toward opposite poles of the cell (loss of tubulin)
triggered by APC
describe APC in anaphase
Anaphase promoting complex
=promotes destruction of cohesin proteins
-securin is normally bound to separase
-APC marks securin with ubiquitin and destroys it
-separase is no longer bound to securin and so is activated
- active separase cleaves cohesins and allows for separation of sister chromatids
kinesins are in between the ___ while dyneins are anchored to ___ ____
in between MTs while dyneins are anchored to cell cortex
what causes spindle poles in anaphase to push apart
kinesin and dynein push MT in opposite directions, causing spindle poles apart
what happens in telophase
dephosphorylation of lamins triggers reformation of nuclear envelope
3 types of spindle microtubules
kinetochore - interact with kinetochores
interpolar -interact in middle
astral - extend toward cell cortex
compare chromosomes being pulled apart vs poles being pushed apart in anaphase
chromosomes being pulled apart = kinetochore MTs shorten and so chromosomes are pulled to opposite sides
poles being pushed apart = interpolar MTS slide and pull spindle poles apart *kinesin and dynein push in opposite directions
