1- Cell division 23 Oct
1- microtubule will connect directly to the DNA
3 different cytoskeletal
microtubule makes mitotic spindle
intermediate filament
they will rearrenge their position as well as the position of DNA throughout the cell division using kinesin and dynein
the nuclear lamina has to change their assembly throughout the cell division
actin filament
one extreme eg. of actin filament changes during cell division is a contractile ring form at the end of the cell division which is in the cytokinesis phase
key proteins during mitosis
M phase of the cell cycle
2- phases of the cell cycle
s phase: synthesising DNA to double
centrosome is sinthesized to become 2
so each daughter cell can have a centrosome
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interphase
consists of G1 , S and G2 phases
what happens at interphase:
s phase: replication of DNA and replication of centrosome
in interphase the morphology wise cell looks like to the one on the right hand side
- NOT very condensed brown DNA siting everywhere whitin the nucleus
- one centrosome light green centre of mictotubule
-dynamically growing and shrinking microtubules - No interaction between nucleus and microtubule
at the end of the enterphase right before going to actual dividing phase
you need to have double the content of DNA whithin the nucleus
flowing around everywhere
a pair of centrosome so they can divide into 2
why do you think DNA is floating everywhere in nucleus rather than being compact as sister cromatid?
better to be uncoiled to be transcribed to make protein
DNA has to be read into messenger RNA and then protein
so if it is hardly coiled you need to uncoil it everytime you do any work so makes sense not to have any condensed DNA form within the nucleus
but when you divide into 2 if it is not hardly coiled then they would be a lot of mistake >>> mutation will happen >>> cancer
mitosis
pro phase is the first phase
a little of condensation happening
a little bit of white parts in the nucleus symbolising DNA becoming of coiled structure
mitosis spindle forming --- ⁉ being ready
prometaphase
nuclear envelop will be gone
microtubule can go in and start interacting with the sister chromatid>>> the coiled condensed form of DNA
metaphese
they finish connecting the microtubule to the sister chromatid
they are ready to pull then away
anaphase
pull microtubule away from eachother
devide the pair , each twards the centrosome
telophase
finished with pulling them apart
protect DNA information within nucleas envelope
forming a nulear envelop
see a little bit of actin ring
cytokineses
you can pinch out and
dived into 2 cell membrane
3- cell division- protein changes
cyclin changes
before s phase
G1/S- cyclin shoots up
during s phase
S-cycling will shoots up
before metaphase to anaphase
M-cyclin will shoot up
4- interphase
normal state of the cell
in the resting period so they are not growing
we have non condensed cromosome= decondensed in the nucleus sitting everywhere
right before the cell division should be double the content of
right after the cell division if they went through the sphase
and duplicated centrosome (after sphase)
if there is only one centrosome that means interphase before the s phase
we have normal microtubule in the cytoplasm
5- phrophase
condensing the DNA into more condensed form of chromosome
you will see a kinetochore which is usually in the centre of the chromosome where the centrosome actually make the binding
cenrtosome will form the mitotic spindle between them
you still have nuclear envelop
we have NOT finish the job of condensing chromosome
6- prometaphase
nuclear envelop will be gone
microtubule can access to the actual chromosome
they try and error to make the perfect binding to the kinetochore
one kinetochore has to bind to one centrosome and the other side of that pair has to be bound to the centrosome attach to the other side of the centrosome
there will be a lot of trial and error
7- meta phase
complete that trial and error and you make perfect binding through the kinethochore from either side of the centrosome at spindle pole
you have all the sister chromatids at the equator of that spindle pole
you have all DNA nicely condensed and lined at the middle line
no nuclear envelop
8- Anaphase
nuclear envelop not there
you pull each pair towards each pole of the centrosome
you see 2 groups of chromosome rather than one in the middle at metaphase
11- Mitotic spindle
9- Telophase
they are warping those DNA information within nuclear envelop , so they dont make any mistakes
you start seeing nuclear envelop structure
which is not perfect yet
there will be still a centrosome, interpolar microtubule still existing to control the position of these 2
if you dont have the middle green ones as interpolar microtubule
you dont have a great control of each centrosome, they might interact together and there might be a mix of the chromosome betw. those 2 which is not good
10- cytokinesis
dividing into 2 cells
contractile actin myosin ring form in the middle ,
they pinch it and it becomes 2 separate entity
interpolar microtubule will be gone soon
micro tubule structure
the pic is metaphase because chromosomes are nicely in the middle
we call this centrosome spindle pole
ASTRAL microtubule ⭐ does not interact with microtubule from the other side of the centrosome
they are helping positioning the spindle pole
interacting with the other portion or cell membrane
Kinetochore microtubule ⭐
we have microtubules interacting with microtbules from other side through kinetochore
impor. role : making perfect binding so they can do the job of dividing the chromosome into same 2 portions
interpolar microtubule ⭐
direct interaction
there are a lot of dynein and kinesin
interpola mic. will help positioning the spindle pole to the other spindle pole , so you push it away then cenrtosome will be further apart
if you want to pull them then centrosome will be closer to eachother
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12-major motor proteins of the spindle
a lot of dynein and kinesine work together with microtubule to control the position of the
1- pole
2- kinetochore bound DNA portion
3- their distance
dynein moves to minus end that helps making the distance between cell membrane to the centrosome closer
Kinesin -14 in the interpolar microtubule is the only exception of the kinesin moving to minus end
kinesin 4, 10 and 5 all move to plus end
kinesin 14 move to minus end
will pull the centrosome closer to theother centrosome
interesting looking kinesin which has 4 heads
kinesin 5 will move to plus end in both sides
that is going to be very efficient puting 2 centrosome together closer to eachother
kinesine 4,10 is important to make perfect binding of kinetochore microtubule to the kinetochore
use kinesin 4 and 10 and move around the actual chromatin chromosome to be able to put in the right position
kinetochor microtubule to make perfect binding
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13- what is doubling during the s phase
nuclei and centrosome
14- kinetochore and chromosome attachment
mechanism to explain how microtubule make perfect binding to the kinetochore
it is theory, it is not being totally proven
one of the explanations scientists came up with alot of evidences
microtubule just randomely going near the sister chromatid
those structure crossing with anti parallel cross linking at a nucleation level and then later they form some actual antiparallel structure with some kinesin and dynein and other types od kinesin will come in and move around those actual chromatin to the minus or plus end so they can fing the edge of microtubule which they have to actually bind
diagram on the bottom right:
energy wise when you dont have pathic ??? binding from the microtubule from the either side >>> it is enegetically not very stable
when kinetochore microtubule make a perfect binding to the kinetochore from either side will be more stable
keep trying until they find the perfect binding stats
15- the important protein is APC/C
there will be:
securin
cohesin
peparase
APC/C protein will kick in when anaphase has to happen
until the metaphase the 2 chromosome has to be perfectly paired
that is the job of protein cohesin ⭐
a ring structure wrapping around 2 sister chromatids so they are pair
when APC kicks in it will degrage the securin which secure the inactive form of separase
APC/C ⭐ will degerade the securin then inactive seperase can become active
Active separase will seperate the cohesin
there is no more ring so the kinetochore microtybul or interpolar microtubule pull away those sister chromatids into either side of the pole
the impo. is having the contractile ring
very concentrated levels of protein actin and myosin at the ring
it becomes smaller and smaller
you find a lot of cleavage furrow structure
that is the midbody right before they are aparting
another protein=formin
RhoA pathway will activate both formin and the Rock
which will end up promoting the actin filament formation as well as myosin 2 activation which will both work together
to make the contractile ring become more contractile so they can pinch out into 2 separate entity
16 - nuclear envelop
in the interphase you have nice intact nuclear envelop
because you dont want to loose any DNA to the cytosole
as soon as prometaphase happens all the nuclear envelop structure will be gone so microtubial can come in and intract with the chromosome
until telophase, more structured nuclear envelop forming in telophase
but not totally intact as interphase but at the end of the cell division you'll get the nuclear envelop back to normal again
if you want to stain nuclear lamina, during cell division, you should be able to draw what that staining look like through out cell division
summary slide has the key pints in cell division