Mitosis Flashcards
name the stages of mitosis
prophase, prometaphase, metaphase, anaphase, telophase
prophase
chromosomes condense and become visible
bipolar spindle develops
prometaphse
nuclear envelope dissolves
chromosomes begin to migrate to equatorial plane (metphase plate) and are seen to contain two chromatids
kinetochore forms
metaphase
chromosomes are fully condensed and located at metaphase plate
anaphase
each centromere splits
the two chromatids of each chromosome are pulled to opposite poles
telophase
chromosomes reach poles and start to decondense
nuclear membrane reforms due to dephosphorylation of the lamins and other nuclear envelope components
chromosome surface is necessary to reassemble the nuclear components
cytoplasm starts to divide
G2-M transition
regulated by Cyclin B1/Cdk1
after complex formation, rapidly phosphorylated by Cdk-activating kinase (CAK, activating) and Wee1 (deactivating)
Cdc25 fully activates the complex by removing the inhibitory phosphorylation
blocking of export form the nucleus allows for a rapid build-up and trickers mitosis
Cyclin A/Cdk2 also phosphorylates subunits of the condensing complex and helps with chromosome condensation and microtubule assembly

mitotic cyclin positive feedback
active M-Cdk activates more active Cdc25 phosphatase

Describe some of the regulatory pathways in the DNA damage checkpoint.
Cdc2 is the old name for Cdk1
phosphrylation of CHK2 and CHK1 by ATM/ATR leads to inactivation of the Cyclin B/Cdk1 complex until DNA damage is resulved
p53 is also activated along with BRCA1
14-3-3 is an adaptor protein that binds to Cdc25 and exports it into the cytoplasm

disassembly of the nuclear envelope during prophase/prometaphase
phosphorylation of nuclear envelope, core complexes, lamins, etc. causes it to fall apart
nuclear envelope gets subsumed into the ER
transcription and translation are shut off through phophorylation as well
the Golgi becomes fragmented as well
condensin
a complex of several proteins that form a circular structure and introduces superhelical twists into the DNA
DNA topoisomerase is present to disentangle entwined sister chromatids
Aurora B kinase
phosphorylates Histone H3
histone H1 is also phosphorylated by Cdk1
kinetochore
a complex protein structure that forms in the middle of the chromosome at the centromere
one on each sister chromatid, face opposite to each other
microtubules attach to this structure

microtubule spindle formation
requires at least 7 kinesins and dynein
a combination of kinetochore microtubules, interpolar microtubules, and astral microtubules
asters radiate out of the centrosomes, associate with each other through kinesin motor proteins, also associates with the cortex of the cell

kinetochore microtubules
plus ends embedded in the kinetochore and minus ends in the spindle pole
form bundles of 20 microtubules called kinetochore fibers
interpolar microtubules
long microtubules extending across the length of the spindle, but not necessarily associated with the spindle poles
arranged in an antiparallel array
astral microtubules
radiate from the spindle poles and help orient the spindle in relation to the cell cortex
erroneous spindle attachments
amphitelic - normal attachment
monotelic - one attaches before the other, resolved very quickly
syntelic - single spindle attaches to both kinetochores
merotelic - a single sister chromatid attaches to both spindles

microtubule treadmilling at the kinetochore
happens during metaphase
poleward state, dissociation of GDP-bound tubulin from shortening end, centromeres stretch
neutral state, association of GTP bound tubulin of growing end
kinetochore proteins such as chromokinesin can sense the tension and ensure that the chromosomes align equally at the metaphase plate

spindle assembly checkpoint
even a single improperly attached kinetochore can send out strong signals to prevent anaphase from happening
APC (anaphase promoting complex) is activated once the checkpoint is passsed
APC ubiquitinylates the securin protein, releasing separase, which can then degrade the cohesion complex

APC
E3 ubiquitin ligase, leads to the degradation of cyclins during anaphase, tirggers events in anaphase
leads to degradation of securin, freeing separase to degrade the cohesion complex

Anaphase A
the kinetochore fibers shorten, moving the chromatids toward the poles

Anaphase B
the spindle elongates and the poles separate due to motor driven interactions between interpolar microtubules and intrinsic mobility of the poles themselves

cytokinesis
process that divides the mitotic cell into two daughter cells
contractile ring has an actin-myosin complex that is regulated by local release of calcium, which activates the myosin light chian kinase, activating myosin II in the ring
the cleavage furrow forms where the plasma membrane is constricted and the cell pinches in two
the cytoplasmic bridge forms a highly ordered array of microtubules and components from the central spindle called the midbody
eventually the cells separate and the midbody is lost, but in spermatogenesis, the cell’s don’t seaparate the the midbody becomes a ring canal
