w11 txtbk Flashcards
cell cycle
process where cell duplicates its contents and divides into 2
M phase
period of the eukaryotic cell cycle during which the nucleus and cytoplasm divide to produce 2 daughter cells
interphase
long period of the cell cycle b/w one mitosis and the next
-includes G1 phase, S phase and G2 phase
S phase
s=synthesis
period during euk. cell cycle where DNA is synthesized
-flanked by 2 “gap” phases called g1 and g2 during which the cell continues to grow
g1 phase
falls b/w end of cytokinesis and start of DNA synthesis
g2 phase
falls b/w the end of DNA synthesis and the beginning of mitosis
what would happen if interphase lasted only long enough for DNA replication
the cell wouldn’t have time to double its mass before it divided
cell-cycle control system
guarantees that the events of the cell cycle
(DNA rep., mitosis…) occur in a set sequence and that each process finishes before next one starts
-to control this, the system is regulated at certain critical points of the cycle by feedback from the process currently being performed
–cannot be delayed
how is mitosis or cell division delayed
if needed, control system employs a set of molecular brakes called checkpoints, to pause the cycle at certain transition points
-this way, it doesn’t trigger next step until cell is properly prepared
late g1 phase
control system confirms that the environ. is favorable for proliferation before moving on to replicate DNA
if conditions unfavorable:
-cells can delay entry into cell cycle and can enter specialized resting state called G0
sometimes referred to as start
transition from G2 to M phase
control system confirms the DNA is undamaged and fully replicated
-ensuring the cell doesn’t enter mitosis unless dna is intact
transition midway through mitosis
cell cycle control machinery confirms the duplicated chromosomes are properly attached to cytoskeletal machine (called mitotic spindle)
-before the spindle pulls the chromosomes apart and segregates them into 2 daughter cells
why is the g1 phase important in animals
point in cell cycle where control system is regulated by outside influences
-signals from other cells stimulate cell proliferation when more cells are needed and block it when not needed
explain the different parts of the cell cycle
s phase- cell replicates dna
m phase- where mitosis occurs, followed by cytokinesis
g1 and g2- 2 gap phases between S and M phases, when the cell continues to grow and make preparations for the next phase
cell-cycle control system
network of regulatory proteins that govern the orderly progression of a eukaryotic cell thru stages of cell division
how does the cell cycle control system govern the cell cycle
by cyclically activating and then inactivating the key proteins and protein complexes that initiate or regulate dna rep, mitosis and cytokinesis
this regulation carried out thru the phosphorylation and dephosphorylation of proteins (switching the activity of a protein on and off)
phosphorylation rxns that control cell cycle
carried out by protein kinases, while dephosphorylation is performed by a set of protein phosphatases
kinases at the core of the cell-cycle are present in proliferating cells
-activated only when needed
-activity of each occurs in cyclical fashion
cyclin function
regulatory protein whose conc. rises and falls at certain times during cycle
-help control progression from one stage of cell cycle to next by binding to cyclin-dependent protein kinases (dks)
cyclin-dependent protein kinase (Cdk)
enzyme that when complexed with regulatory cyclin protein can trigger various events in the cell-division cycle by phosphorylating specific target proteins
-the cyclical changes in cyclic concentrations help drive the cyclic assembly and activation of the cyclin - Cdk complexes
-once activated, cyclin-Cdk complexes help trigger cell cycle events (eg entry into S or M phase)
what occurs in transition points throughout cycle
control system monitors cell’s internal state and external conditions before allowing cell to continue thru cycle
For example, it allows entry into the cell cycle and initiation of S phase only if environmental conditions are appropriate; it triggers mitosis only after the DNA has been completely replicated; and it initiates chromosome segregation only after the duplicated chromosomes are correctly aligned on the mitotic spindle
how does the control system monitor and slow progress at transition points
at start transition in late G1 phase, it uses Cdk inhibitors to keep cells from entering cell cycle
at G2 to M transition, it suppresses activation of M-Cdk by inhibiting the phosphatase required to activate Cdk
-can also delay chromosome segregation in mitosis by inhibiting the activation of APC/C
=prevents degradation of M-cyclin and other
regulators
how do cyclin-Cdk complexes trigger different stages of cell cycle
kinase activity of cdk subunit increases at different stages of cycle
g1 phase
important time of decision-making for cell
-based on intracellular signals that provide info
about the size of cell and extracellular signals reflecting conditions in the environ,
machinery can either hold cell transiently in G1, direct it to withdraw into a more prolonged nonproliferative state(G0)
or
allow it to prep entry into another cell cycle
if errors occur during dna rep, how does the cell keep from dividing with dna thats incorrectly or incompletely replicated
cell control system uses mechanism that can delay entry into M phase
-for cell to progress into mitosis, inhibitory phosphates must be REMOVED by activating protein phosphatase called Cdc25
–if DNA rep stalls, the presence of single-stranded DNA at replication fork triggers DNA damage response
-part of this response includes inhibition of the phosphatase Cdc25, which PREVENTS the removal of the inhibitory phosphatases from M-Cdk
–as a result, M-Cdk remains inactive and M phase delayed until DNA rep is complete and any DNA damage is repaired
the inactivation of M-Cdk prevents what
prevents the onset of M phase
sister chromatids
copy of chromosome, produced by DNA rep, that still remains bound to other copy
cohesins
ring shaped SMC protein complex that organizes interphase chromosomes into a long series of large chromatin loops
-special subset of cohesins holds tg sister chromatids after dna has been replicated
what occurs after the 2 duplicated chromosomes have condensed?
2 complex cytoskeletal machines assemble in sequence to carry out major mechanical processes that occur in M phase
-mitotic spindle carries out nuclear division(mitosis) and in animals cells, the contractile ring divides entire cell into 2 (cytokinesis)
mitotic spindle structure and function
composed of microtubules and the various proteins that interact with them, including microtubule-associated motor proteins
responsible for pulling duplicated chromosomes apart and allocating one copy of each chromosome to each daughter cell
M phase
first 5 stages constitute mitosis (prophase, prometaphase, metaphase, anaphase, telophase)
cytokinesis- final stage of M phase
what does the phosphorylation of Cdc25 by M-Cdk do?
Activates Cdc25, which in turn activates more M-Cdk
-When phosphorylated, Cdc25 becomes activated, which in turn removes the inhibitory phosphates from M-Cdk, thereby activating more M-Cdk
centrosome
microtubule-organizing center that sits near the nucleus in an animal cell
during cell cycle, this structure duplicates to form the 2 poles of the mitotic spindle
duplication is needed for centrosome to be able to help form the 2 poles of the mitotic spindle, and allows each daughter cell to receive its own centrosome
centrosome duplication
begins at the same time as dna rep, and the process is triggered by the same Cdks, Cdk- that initiate dna replication
Initially, when the centrosome duplicates, both copies remain together as a single complex on one side of the nucleus
aster
as mitosis begins, 2 centrosomes separate and each nucleates a radial array of microtubules called aster
the 2 asters move to opposite sides of nucleus to form the 2 poles of mitotic spindle
microtubules and dynamic instability
continuously polymerize and depolymerize by the addition and loss of their tubulin subunits: individual filaments alternate b/w growing and shrinking –> dynamic instability
new microtubules generated to balance the loss of those that shorten until they disappear
at the start of mitosis, why does dynamic instability increase?
M-cdk phosphorylates microtubule-associated proteins that influence microtubule staility
as a result, rapidly growing and shrinking microtubules extend in all directions from the 2 centrosomes, and new microtubules sprout from sides of existing microtub.
mitotic spindle
array of microtubules and associated molecules that form b/w opposite poles of a euk. cell during mitosis and pulls apart duplicated chromosome sets
spindle poles
centrosome from which microtubules radiate to form mitotic spindle
before M phase
-cell increases in size
-dna of chromosomes are replicated and centrosome is duplicated
prophase
duplicated chromosomes(each w/ 2 sister chromatids) condense
-outside nucleus, the mitotic spindle assembles b/w 2 centrosomes, which start moving apart
prometaphase
starts abruptly with the breakdown of the nuclear envelope
-chromosomes can now attach to spindle microtubules via their kinetochores and undergo active moment
metaphase
chromosomes are aligned at the equator of spindle, midway b/w spindle poles
-microtubules attach to opposite poles of spindle
anaphase
sister chromatids synchronously separate and pulled slowly twd spindle pole to which they’re attached
shorter microtubules contribute to chromosome segregation
telophase
the 2 sets of chromosomes arrive at poles of spindle
-new nuclear envelope reassembles around each set
division of cytoplasm begins with the assembly of contractile ring
cytokinesis (animal cell)
cytoplasm is divided in 2 by contractile ring of actin and myosin filaments, which pinches cell into 2 daughters, each with one nucleus
what triggers the disintegration of the nuclear envelope
process triggered by the phosphorylation and consequent disassembly of nuclear pore proteins and the intermediate filament proteins of the nuclear lamina
how do sister kinetochores know that they’re attached correctly
the attachment to opposite poles (bi-orientation) generates tension on the kinetochores, which are being pulled in opposite directions
this tension signals that they’re attached correctly and ready to be separated
how do chromosomes help with the assembly of the mitotic spindle
they stabilize and organize microtubules into functional mitotic spindles
what event defines the beginning of metaphase
when the duplicated chromosomes(attached to mitotic spindle) become aligned at equator of spindle, halfway b/w the 2 spindle poles, forming the metaphase plate
whats required to maintain the metaphase spindle
continuous balanced addition and loss of tubulin subunits required
when tubulin addition to the ends of microtubules is blocked by the drug colchicine, tubulin loss continues until metaphase spindle disappears
how does anaphase begin
with the breakage of the remaining cohesin linkages that hold tg the sister chromatids in the duplicated chromosomes
this release allows each chromosome to be pulled twd the spindle pole to which its attached
-the movement segregates the 2 identical sets of chromosomes to opposite ends of the spindle
separase function
protease that destroys cohesin linkage
securin function
before anaphase begins, protease held in inactive state by inhibitory protein called securin
-at beginning of anaphase, securin is targeted for destruction by APC/C (same protein that marks M-cyclin for degradation)
once securin has been destroyed, separase is then free to sever the cohesion linkages
chromosome movement in anaphase A vs anaphase B
A- kinetochore microtubules shorten and the attached chromosomes move POLEWARD
–driving force thought to be provided by the loss of tubublin subunits frm bothe nds of kinetochore microtubules
B- spindle poles move apart, further segregating the 2 sets of chromosomes
–driving forces provided by 2 sets of motor proteins(members of kinesin+dynein) operating on diff types of microtubules
kinesin proteins and microtubules
act on the overlapping non-kinetochore microtubules, sliding the microtubules from opposite poles past one another at equator of spindle and pushing spindle poles apart
dynein proteins and microtubules
anchored to the PM, and move along astral microtubules to pull poles apart
how does the cell monitor chromosome attachment?
makes use of a negative signal
-kinetochores of unattached chromosomes send a “stop” signal to the cell-cycle control systen
–this signal inhibits further progress thru mitosis by blocking the activation of APC/C
w/o active APC/C, sister chromatids remain glued tg
-so no duplicated chromosomes can be pulled apart until every chromosome has been positioned correctly on mitotic spindle
how can mitosis be prolonged?
absence of APC/C activity also prevents destruction of cyclins, so that Cdks remain active, thus prolonging mitosis
what does the spindle assembly checkpoint control
the onset of anaphase, as well as the exit from mitosis
what happens during the process of telophase
nuclear pore proteins and nuclear lamins that were phosphorylated during prometaphase are now DEphosphorylated, which allows them to reassemble and rebuild nuclear envelope and lamina
-once envelope has been reestablished, pore restore the localization of cytosolic and nuclear proteins and condensed chromosomes decondense into their interphase state
–new nuc. has been created, and mitosis is complete
–all that remains is for the cell to complete division
how does APC/C trigger onset of anaphase
triggering the cleavage of cohesins that hold sister chromatids together
