Week 12 Textbook Flashcards
what is the cell cycle
the orderly sequence of events by which a cell duplicates its contents and divides into 2
what is cytokinesis
when the cell splits itself into 2 new daughter cells
what is the M phase
where the nucleus and cytoplasm divide to produce 2 daughter cells
what phases does interphase include
g1, s phase, g2 phase
S phase = synthesis, the dna is replicated
G1 phase = falls between the end of cytokinesis and the start of DNA synthesis
G2 phase = falls between the end of DNA synthesis and the beginning of mitosis
- during the gap phases, it monitors the internal and external environment so that it has the proper conditions for reproduction and if they should continue to the next phase or allow more time to prepare
what happens during interphase
A cell grows, transcribes genes, synthesizes proteins, grows in mass
the phases allow the cell to enlarge, duplicate
- without the phases, the cell would not have enough time to double in mass before it divided
what is the first division after fertilization called
cleavage division
can you explain the cell cycle control system
to make sure that the dna is replicated and divide properly
- regulated via feedback from certain points in the cycle = checkpoints so that the control system does not trigger the next step in the cycle unless the cell is properly prepared
EX: the completion of the S phase must trigger the beginning of the M
if dna is damaged, the cycle = on hold
what happens if the environment is unfavourable for cell proliferation
needs sufficient nutrients and specific sigal molecules in the extracellular environment
if = unfavourable = delay enter in the cell cycle and can enter a specialized resting state known as G zero = can be referred to as the start
- start is the important transition state and it happens at the end of g1 as it continues to the S phase
what is the second major transition state
between G2 to M phase
making sure all DNA is replicated from the S phase and making sure all the DNA that was damaged is fixed
what is the third transition state
midway thru mitosis
confirms that the duplicated chromosomes are properly attached to a cytoskeletal machine called the mitotic spindle - before it pulls them apart and puts them into 2 daughter cells
how does the cell cycle control system prevent cancer
the Start transition in late G1 - the signals from the other cells if needed will stimulate the cell proliferation and if they do not need more cells they will block cell proliferation which prevent it from moving to the next phase
it regulates the cell number in the tissue of the body
t/f all eukaryotic cells have similar machinery and control mechanisms
true
this is why we can study a wide variety of organisms
how do u switch a protein on and off
by phosphorylating and dephosphorylating
phosphorylating = protein kinase
deephosphorylation = protein phosphatases
explain the function of protein kinases in the cell cycle control system
they are activated when needed and quickly inactivated
become active toward the end of the g1 phase and are responsible for driving the cell into S phase
the other kinase becomes active just before the M phase and drives the cells into mitosis
the progression of the cell cycle depends on _____
cyclin-dependent protein kinases (Cdks)
Cdk is attached to a cyclin molecule = activation to initiate particular steps
the cyclin molecules also helps direct the Cdk to the target proteins that the Cdk phosphylates
what are cyclins
they have no enzyme activity on their own but they need to bind to the cell cycle kinases before they can become active
= cyclin-dependent protein kinases or Cdks
why is it called cyclins
because the concentratoin change are cyclical
the cyclical changes in the cyclic concentrations help drive the cyclic assembly and activation of the cyclic-Cdk complexes
- more concentration during mitosis rather than interphase
explain in detail the G1 phase
depending on the extracellular signals reflecting conditions in the environment, the control machinery can either hold the cell in g1, g zero or into another cell cycle or terminally differentiation
once it passes the start state it usually contines smoothly
the cell is filled with active cyclin-cdk complexes - specially S-Cdks and M-Cdks. These complexes must be turned off by the end of mitosis. Why?
to allow the cell to properly finish dividing
prevent the cell from immediately starting another division without taking a break in the g1 phase
how does the cell transition from M phase to G1 phse
destroying all exisiting cyclins so that cdks cannot be activated
stop making new cyclinc - to prevent new cdks from being activated
use cdks inhibitor proteins to block any remaining activity
this ensures that it doesn’t rush into dividing again before it is ready
what is the origins of replication and what does it do for the cell cycle
serves as landing pads for the proteins and protein complexes that control and carry out DNA synthesis
- it recruits a protein called Cdc6 whose concentration rises early in g1
together these proteins position the helicase
- the signal to commence replication comes from s-cdk - the cyclin-cdk complex that triggers s phase
s-cdk is assembled and activated at the end of g1 - triggers the binding of all the other proteins needed for replication
- also prevents the re-replication
it does this be phosphorylating both cdc6 and ORC - inactivating the proteins prevents helicases from reloading onto the origin of replication pads
when Cdks are inactiviated in the next g1 phase, the ORC and Cdc6 are reactivated - this allows the origins to be prepared for the s phase
how does the cell keep from dividing with DNA that is incorrectly replicated
the cell cycle control system delays entry into the M phase
the activity of m-cdk is inhibited by phosphorylation at particular sites - to progess into mitosis these inhibitiry phosphates must be removed by an activating protein phosphatase called cdc25
if dna replication stalls the presence of single stranded dna at the replication fork triggers a dna damage response = inhibition of the phosphatase cdc25 - this prevents the rmoval of the M-cdk
therefore, m-cdk remains inactive and M phase is delayed until the dna is complete and fixed –> g2 -> m phase
t/f the activation of s-cdk helps prevent the onset of M phase
false
the activation of s-cdk does not prevent hte onset of M phase
it is the inactivation of m-cdk which prevents the onset of Mpahse
what are sister chromatids
when a chromosomes is duplicated and the eo copies remain tighly bound together
held together by cohesins - these assemble along the length of each chromatid as the DNA is replicated
without proper cohesins = issues with segragation
explain how chromosomes condensation occurs via condensins
the condensin = ring shaped SMC protein that compacts duplicated chromosomes for segregation by forming both loops and loops within loops
- assemble along each individual sister chromatid helping each of these double helices to coil up
what is the contractile ring
divides the entire cell into 2 = cytokinesis
- based on actin and myosin
- arranged at the equator of the cell
starts to assemble just beneath the plasma membrane toward the end of mitosis
mitotic spindle is based on actin t/f
false
it is based on microtubules
what are the 5 stages in mitosis
prophase
prometaphase
metaphase
anaphase
telophase - cytokinesis
before m phase begins - what are the 2 critical events that need to be completed
dna needs to be fully replicated
the centrosome must be duplicated
what is the centrosome
it is the principal microtubule organizing center in animal cells
the duplication is necessaet for the centrosome to be able to form the 2 poles of the mitotic spindle which allows each daugther cell to recieve its own centrosome
when does centrosome duplication occur
at the same time as dna replication
the process is triggered by the cdks which initiate the dna replication
as mitorsis begins the centrosomes that were formed only on one side move to the opposite ends
- each of them nucleate a radical array of microbtubules called aster
- rapdily growing and shrinking microtubules extend in all directions from the 2 centrosomes
what is a kinetochore
some microtubules may attach to a chromosome at its kinetochore
a protein complex associated with each sister chromatid - the kinetochore microtubules are central players in chromosome segregation
what are interpolar/non-kinetochore microtubules
short microtubules in constact elgonation and collaspsing, making and breakign connections - driven in part by interactions with motor proteins and other microtubules form a dense gel like meshwork which is the basic framwork of the mitotic spindle
t/f the centrosomes on either side of the cell become called the spindle poles
true
and they have astral micotubules coming out from it
what are the 3 kinds of microtubule that come out of the mitotic spindle
kinetochore microtubule
non-kinetochore microtubule which are sacttered arround the spindle
astral microtubules
overview of prophase
duplicated chromosomes each consisiting of 2 sister chromatics = condense
mitotic spindles assembles and move apart
overview of prometaphase
breakdown of the nuclear envelope
chromosomes can now attach to the spindle microtubules via their kinetochores
the process of the dissolving of the envelope is triggered by the phosphorylation and disassemble of the nuclear pore proteins and the intermediate filament proteins of the nuclear lamina
overview of metaphase
chromosomes are aligned at the equator of the cell
midway between the spindle poles
the kinetochore micotubules on each sister chromatic attach to the oppoiste poles of the spindle
overview of anaphase
sister chromatics are separated and pulled slowly towards the spindle poles that they are attached to the kinetochore microtubules get shorter and the spindle poles move further apart
- breakage of the cohesin linkages that hold the chromosomes together
- the cohesin is destroyed by a protease called separase
- separase = inactive state by an inhibitory protein called securin - once securin has been destroyed (ubiquitylation), the separase is free to sever the cohesin linkages (now active)
overview of telophase
the two sets of chromosomes arrive at the poles of the spindle
new nuclear membrane forms around each set
this completes the formation of 2 nuclei and marking the end mitosis
the division of cytoplasm begins starting with the assembly of the contractile ring
overview of cytokinesis
in the animal cell
the cytoplsma is divided by the contractile ring of actin and myosin filaments
t/f the kinetochore binds to the plus end of the microtubule
true
the kinetochore is binded to the centromere part of the chromosome and has the kinetochore microtubules to bind to it at the plus end
what happens if the centrosome dna sequence is altered
no kinetochore binding
fail to segregate
what does bi orientation mean
when the attachment is opposite poles
this generates tension on the kinetochores which are pulled in opposite directions
(remember the kinetochores are attached to either sister chromatid at their centromere (the dip in the middle of the chromosome)
t/f a continuous balanced addition and loss of tubulin subunits is needed to maintain the metaphase spindle
true
what happens when the drug colchicine blocks the addition of tubulin
no more tubulin addition
tubulin loss continues until the metaphase spindle disappears
what happens if one end of the kinetochore attachments are severed during metaphase
the entire chromosomes immediately moves towards the pole to which is remain attached
what would happen if the attachment between 2 sister chromatids is cut
the two opposite chromosomes separate and move toward opposite poles
shows that they are moved to the middle = metaphase plate under tension
explain the differences in anaphase A and anaphase B
anaphase A = kinetochore microtubules shorten and the attached chromosomes move poleward - the chromatids are pulled to the poles
- the driving force = the loss of tubulin subunits from both ends of the kinetochore microtubules
anaphase B = the spindle poles themselves move apart - further segregating the 2 sets of chromosomes
- microtubule growth at plus end of non-kinetochore microtubules also help push the poles apart
- driving force = motor proteins in the kinesin and dynein families
kinesins proteins act on the overlapping non-kinetochore microtubules
dynein proteins anchored the plasma membrane, move along the astra microtubules to pull the poles apart
what happens if the cell were to proceed into anaphase before all chromosomes were connected to the spindle
one cell would = less chromosomes
one cell = surplus
to make sure - the cell makes use of a negative signal - the kinetochores of unattached chromosomes send a stop signal to the cell cycle control system
the signal inhibits further progress of mitosis by blocking the activation of APC/C
- the spindle assembly checkpoint thereby controls the onset of anaphase as well as the exit from mitosis
explain the reformation of the nuclear envelope in telophase
vesicles of nuclear membrane surround these chromosome clusters and then fuse to re-form the nuclear envelope
the nuclear pore proteins and nuclear lamins were phosphorylated during prometaphase, now they are dephosphorylated which allows them to reassemble and rebuild the nuclear envelope and lamina
inside the nucleus contains decondensed chromosomes
what is APC/C
anaphase-promoting complex OR cyclosome
it triggers the anaphase by activating separase - which is a protease that cleaves the cohesins that hold the sister chromatids
what is the cleavage furrow
cuts between the two groups of segregated chromosomes
so that each daughter cell receives an identical and complete set of chromosomes
- formed by the contractile ring underneath the plasma membrane
how does the mitotic spindle dictate the position of the cleavage furrow
during anaphase, the overlapping microtubules that form the central spindle recruit and activate proteins that signal to the cell cortex to initiate the assembly of the contractile ring
what is the contractile ring made out of
made of overlapping array of actin filaments and myosin filaments
assembles in anaphase - and is attached to membrane-associated proteins on the cytosolic face of the plasma membrane
large force produced
what is the substratum
the surface that cells grow on or attach to
the cell changes shape and adhesion during divison - in interphase they have strong adhesive contacts with the substratum, in M phase, they round upd
integrins are responsible for sticking the cell to the substratum and during M phase, the integrins get phosphorylated which weaken their attachment ability
what is phragmoplast
in a dividing plant cell, the structure containing microtubules and membrane vesicles (dervied from the golgi apparatus) that guides the formation of the new cell wall
- they are specialized microtubule-based structure
how are the organelles separated into the daughter cells
mitochondria and chloroplasts are abundant
- the ER is cut into 2 during cytokinesis
- the golgi apparatus fragments during mitosis and the fragments associate with the spindle microtubules via motor proteins - they hitch a ride into the daughter cells as the spindle elongates in anaphase
what are centrioles
cylindrical array of microtubules usually found as pairs in the centrosome in animal cells
- the other pair is sitting perp to the other one
surrounded by a gel like matrix of proteins
- inside gel = special forms of tubulin = g-tubulin = nucleation site for the growth of one microtubule
although the centrioles do not have roles in nucleation of microtubules - centrioles found in cilia and flagella do nucleate growth in microtubules
what initiates microtubule growth
all of them use y-tubulin ring complexes
by using nucleation sites and keeping concentrations of free alpha/beta tubulin dimers below the concentration that would allow microtubules to form spontaneously
explain meiosis
in specialized germ line cells
somatic cells = diploid which contains 2 copies of every chromosome from the dad and mom
all the chromosomes are duplicated, then they get paired - allows the segregation of homologous chromosomes during the first division
- the 2 duplicated chromosomes within each homolog are then separated during the second meiotic division - this produces 4 haploid nuclei
- the separation = random - each haploid gets a different mixture of mom and dad chromosomes
what is a bivalent
structures formed when a duplicated chromosome pairs with its homolog at the beginning of meiosis
= 4 sister chromatids
2 sister from homologous chromosome 1
2 sister from homologous chromosome 2
- these structures are very stable
how do homologs recognize each other during pairing
not fully understood
probably matching dna sequences on the maternal and paternal chromosomes
what are the 3 parts of interphase and what is the point
g1, s phase, g2
metabolic activity, cell growth, repair
has checkpoints before moving on to the next phase or most importantly into M phase where mitosis and cytokinesis occurs
what kinds of cells do not divide
RBCs, nerve cells, muscle cells
they become differentiation and lose the ability to divide bc there is no nucleus
- some cells only divide when given an appropriate stimulus like when damaged
what kinds of cells divide on an ongoing bassi
hematopoietic and epithelial stem cells
what is the G0 phase
cells that are not dead, but are just not dividing
can go back into the cycle when needed
resting
no profileration
metabolically active
how does the cell cycle control system work
delays later events until the earlier events are completed and done properly
the major checkpoints are
from G1 –> S
G2 –> M
metaphase to anaphase (spindle assembly checkpoint)
if there is issues int he checkpoints is pauses and fixes the issue but without noticing = chromosome segregation defects
what kind of questions do they ask in the G1 –> S checkpoint
is the environment favourable?
the conditions
enough nutrients, specific signals
if no, waits in G0 or G1
what questions are asked in the G2–> M checkpoint
is all the dna replicaed
is the DNA damage repaired
what questions are asked in the metaphase-anaphase transition/checkpoint
are all chromosomes properly attached to the mitotic spindle
what happens if the environment is not favourable to go into the S phase
the cdk inhibitors block entry into S phase
the cdk = cyclin-dependent protein kinase - has a molecular switch called cyclin to activate it
M-cdk is activated by M cyclin and phosphorylates other regulatory proteins
what happens if the DNA is damaged or not replicated to go into the M phase
inhibition of activating phosphatase CDC 25 blocks entry to mitosis
- once CDC 25 is activated it dephosphrylated cdk into M-cdk which moves the cell to mitosis
when cdc25 is activated it removes inhibitory phosphates from CDK1 = turning it one
what happens when the chromosomes are not properly attached to the spindle
inhibition of APC/C activation - this delays exit from mitosis until the chromosomes are ready
- when the continues into mitosis the APC/C is activated
- to stop, it is inhibited from activating
what happens in prophase
the DNA condenses - to be able to see
condenses so it doesn’t damage when it divides
- mitotic spindle assembly starts and requires duplicated centrosomes - requires disassembly and reassembly of MT
- needs to duplicate centrosomes
what is the role of cohesins
they hold sister chromatids together
they also link the centromere of the chromosome (2 sister chromatids) pinched in the center
they are removed from the chromosomes arms except for the centromeres
what is the role of condesins
they loop the DNA again and again to condense
explain the centrosome structure
pair of centrioles in the centrosomes
- placed in perp
- composed of nine fibrils of three microtubules each - short MT fibres in a circle
around the centrioles is a matrix around them = centrosomes
contains gamma tubulin RC as nucleating sites to assemble new MT
- MT minus end is MTOC with the + end of the MT growing and shrinking
how does the centrosome duplicate
the centrosome duplicated initiated in g1 and completed by g2
the centrioles are duplicated and there’s an area where the new centriole grows perpendicular to it and then they separate into their own centrioles
- starting at prophase it separated to the 2 poles - assembly starts in prophase
when does the nuclear envelop breakdown and how does it happen
occurs at the boundary of prophase to prometaphase
- the nuclear lamina (meshwork of interconnected nuclear lamin proteins) + nuclear pore proteins
they all breakdown by phosphorylation - kinase
- triggers the disassembly of nuclear envelope into small vesicles
what happens in prometaphase
the nuclear envelope is now disassembled
the mitotic spindle assembly is complete
the kinetochore MT in the mitotic spindle attach to the duplicated chromosomes and the movement begins
what does the mitotic spindle assembled and function require
microtubule dynamics so the growing and shrinking
the MT motor protein activity like kinesins, cytoplasmic dynein
explain the structure of the completion of the mitotic spindle assembly
- astral MT - connects to the centrosome to help position the mitotic spindle - has cytoplasmic dynein which is the motor protein that moves to the (-) end and is attached to the PM which keeps it anchored
- non-kinetochore MT: cross linked with astral and has kinesin-5 and other proteins holding the NKM together
- has 2 head domains connected to 2 NKM MT and pushes them outwards as they walk towards the + end - kinetochore MT: attach to duplicated chromosomes to the spindle poles (longest and in one tube
how does the kinetochore MT attach to chromosomes
kinetochore are attached at the centromeres of the chromosomes
one kinetochore is attached to the other side (each sister chromatid left+right)
- generates equal amounts of tension on both side and line by the chromosomes at the equator of the spindle for metaphase
kinetochore attached to the sister chromatid has a connecting protein complex that holds the plus end (near middle) so that there is still space on the + end for it to grow and shrink for movement
what occurs in metaphase
all chromosomes are aligned on the metaphase plate known as the equator of the spindle
the microtubule dynamics continue to maintain the metaphase spindle = spindle flux
how does the MT maintain the metaphase spindle
there is a continuous addition of tubulin subunits at the + end
there is a removal tubulin subunits at minus end
the length of kinetochore microtubules does not change bc there is treadmilling
they are shrinking at the minus end which is stuck to the spindle pole and the plus end which is on the chromatic
what happens in anaphase
separation of sister chromatids
- contractile ring starts to form
separase activated and cohesin complex is cleaved
2 types:
- Anaphase A
- kinetochore MT are shortened - loss of tubulin on both ends and sister chromatids are pulled apart to the poles
- spindle poles stays in the same place
- Anaphase B
- spindle poles move outward so the chromosomes already attached to the sister chromatid via kinetochore MT move to the poles as well
*sliding force and pulling force - sliding = kinesin which walks to the + ends of both kinetochore MT that is it attached to via the globular heads
- pulling = cytoplasmic dynein which is attached to the PM which acts as an anchor
what happens in telophase
chromosomes are now separated into their 2 new groups at each spindle pole
- the nuclear enelope now reassembles
- the dephosphorylation of the nuclear pore proteins + lamins (phosphorylation to break apart) - the envelope, lamina and pores reassemble around the DNA
- chromosomes start to decondense, and mitotic spindle disassembles
- the contractile ring is finished in this phase
explain cytokinesis in animal cells
the contractile ring forms in anaphase and is finished in telophase = at the cleavage furrow underneath the membrane
the contractile ring divides the cytoplasm in 2 and is assembled from actin and myosin filaments
- myosin II - pulls 2 separate actin filaments in the opposite direction of their plus end which pulls the actin filaments together around the ring - makes it smaller - contractile force
- cytoplasm is divided
- the ring disassembles once the daughter cells divide
- the interphase microtubules reform
how does the contractile ring know where to assemble
the non-kinetochore microtubules send a signal to the plasma membrane to know where the ring should assemble
t/f plant cells also use centrosomes
false
they use another mechanism to form mitotic spindle
what is phragmoplast in plant cells
forms in the equator of the cell as golgi derived vesicles to form the cell plate
- has MT and AF from golgi
- the vesicles fuse together to form the cell plate
- forms PM between the cells and a cell wall which is cellulose fibers
compare meiosis to mitosis
meiosis
- one round of DNA replication where the chromosomes are duplication
- anaphase 1 and 2 - where the cell division occurs twice (1 = pull homologous chromosomes apart, 2 = pull sister chromatids apart)
- produces 4 randomly assembled haploid cells
mitosis
- one round of replication
- one round of cell division
- produces 2 diploid identical cells
