Lecture 29 Flashcards
Define Condensin and describe it’s function
condesin is a 5 subunit protein complex that contains 2 SMC (structural maintenance of chromosomes) subunits and 3 non-SMC subunits
It forms a ring-like structure and uses ATP to promote compaction and resolution of sister chromatids just before anaphase begins
Name and describe the 3 classes of microtubules
Kinetochore m.:
Interpolar m.:
Astral m.:
Name and describe the attachments of the 3 classes of microtubules
Kinetochore m.: attach each chromosome to the spindle pole
Interpolar m.: hold the 2 halves of the spindle together
Astral m.: interact with the cell cortex
name and describe the 3 forces that work to create chromosome movements.
Depolymerization: of the plus end drives the pulling of the kinetochore towards the pole
Microtubule Flux: microtubules are actively getting dismantled at their plus end (tread-milling on plus end so the length stays the same) which pulls the chromatid towards the pole
Polar ejection: kinesin-4,10 motors on chromosomes walk away from the poles (towards plus end). this action results in a “push-pull” phenomenon
describe how the following are related. APC/c, securin, separase, cohesin.
once everything is prepared/organized enough for anaphase to begin, M-Cdk activates APC/C
APC/C ubiquitinates securin, which destroys it and allows separase to become active
separase cleaves the cohesin from between the sister chromatids and allows them to separate
Describe how the following are related to cell growth. Rb, ATM, Chk1, Chk2, p53, p21 CKI.
Rb: is a tumor suppressing protein that inhibits the action of E2F protein (this protein triggers DNA transcription and entry into S phase)
ATM: (and ATR) is a protein kinase that is activated by DNA damage
Chk1 and Chk2: are both checkpoint kinases that are phosphorylated by (DNA damage activated) ATM
p53 protein: is a major target of phosphorylated Chk1 and Chk2. Activated p53 stimulates the transcription of p21 CKI
p21 CKI: binds to G1/S-Cdk’s and S-Cdks to inhibit the uncontrolled cell division that was caused by DNA damage
(this is all a big system to prevent cancerous growth and fix the damaged DNA)
Describe retinoblastoma
it is caused by a loss/malfunction of both Rb genes, leading to uncheched cell growth in the retina
most cases are diagnosed before age5
For Kinetochore microtubules , describe where their plus and minus ends attach.
The plus ends are attached to the kinetochores of sister chromatid pairs and the negative end is attached to the centrosome
describe the direction it walks, structure, and the role kinesin-5 plays in spindle assembly.
it walks towards the plus end
it has 2 motor domains that interact with the plus end of anti-parallel microtubules
kinesin-5 moves these spindles past each other, in opposite directions
this “forces/pushes” the centrosomes (poles) apart from one another and to opposite sides of the dividing cell
describe the direction it walks, and the role kinesin-14 plays in spindle assembly. explain how kinesin-5 and kinesin-14 work together
it walks towards the minus end
this “pulls” the poles (centrosomes) together
kinesin-5 “pushes” while kinesin-14 “pulls” the poles at the same time
this gives structural integrity to the spindle and effectively orients the poles
Give another name for kinesin-4,10, list the direction it walks, and it’s function.
Chromokinesins
walks toward the plus end
pushes attached chromosomes away from the pole
For astral microtubules , describe where their plus and minus ends attach.
their plus ends radiate out from the centrosome (where negative end attaches) and contact the cell cortex
describe the 3 forces driving chromosomes movement in cell division
Depolymerization: of the plus end drives the pulling of the kinetochore towards the pole
Microtubule Flux: microtubules are actively getting dismantled at their plus end (treadmilling on plus end so the length stays the same) which pulls the chromatid towards the pole
Polar ejection: kinesin-4,10 motors on chromosomes walk away from the poles (towards plus end). this action results in a “push-pull” phenomenon
Describe ataxia telangiectasia
Ataxia = poor coordination Telangiectasia = small dilated blood vessels
The ATM protein is defective in pt’s with this disease, which makes them unable to repair DNA (radiation is especially bad for them)
autosomal recessive genetic condition
How does a lack of Rb protein lead to retinoblastoma?
Rb protein is an inhibitor of E2F protein that stops the cell from entering into S phase
If both copies of the Rb gene are lost (no Rb protein gets made), then there is loss of cell division control and retinoblastoma occurs
What is the Ndc80 complex on a kinetochore?
it is a place where multiple microtubules can connect to the same kinetochore
why is there an “exposed end” of a microtubule that is attached to the Ndc80 complex on a kinetochore? what sort of force is generated at this “exposed end”
so tubulin subunits can either be added or removed as needed
“force pulling” on the kinetochore can occur here when tubulin subunits are removed from the exposed end of the attached microtubule (this moves chromosomes to the pole of the cell)
Describe the term “bipolar attachment” when it is refering to microtubules binding to kinetochores. describe the level of stability that bipolar attachments form, and how that occurs.
bipolar attachment: each sister chromatid is attached to spindles that belong to opposite poles of the dividing cell
only very stable attachements are allowed to occur here, and that is mediated by “kinetochore tension”
Describe the term “bipolar attachment” when it is refering to microtubules binding to kinetochores. describe the level of stability that bipolar attachments form, and how that occurs.
bipolar attachment: each sister chromatid is attached to spindles that belong to opposite poles of the dividing cell
only very stable attachements are allowed to occur here, and that is mediated by “kinetochore tension”
Compare and contrast Anaphase A and Anaphase B.
Anaphase A: chromosomes move apart due to spindle microtubule depolymerization at the kinetochore
Anaphase B: separation of spindle poles themselves occurs via the action of kinesin-5 and dynein motor proteins
Compare and contrast Anaphase A and Anaphase B.
Anaphase A: chromosomes move apart due to spindle microtubule depolymerization at the kinetochore
Anaphase B: separation of spindle poles themselves occurs via the action of kinesin-5 and dynein motor proteins
Name the 4 stages of cytokinesis in order
Initiation
Contraction
Membrane insertion
Completion
Name the 4 stages of cytokinesis in order
Initiation
Contraction
Membrane insertion
Completion
In terms of the role of ATM protein, relate what does not occur in pt’s with Ataxia telangiectasia
ATM senses DNA damage and acts of Chk1 and Chk2
Chk1 and Chk2 activate p53, which arrests the cell cycle
if the DNA damage is mild, repair occurs BUT p53 can trigger apoptosis if the DNA damage is severe
(ATM doesn’t work so none of this happens in AT patients)
