Cell Cycle II (Sept. 15 - Schultz) Flashcards
List the 6 steps of cell replication
- prophase
- metaphase
- prometaphase
- anaphase
- telophase
- cytokinesis
Nuclear membrane is composed of these 2 structural elements…
- Lamin (not to be confused with laminin)
2. Intermediate filaments
How is the nuclear envelope degraded
Lamin is degraded by phosphorylation by M-Cdk. This causes the breakdown during mitosis. Dephosphorylation of the amine reverses this process.
What is the structure of centrosomes?
Pair of centrioles surrounded by pericentriolar matrix
How are centrioles replicated?
At G1: the centriole pairs separate
At S phase: a progeny centriole begins to grow near the base of the parent centriole at a right angle to the original.
The replication is complete by G2 phase.
At M phase the parent/progeny combo separates together as a pair into the mother and daughter cell.
What is an aster and how does it relate to the centrosome?
An ASTER is the radial array of microtubules that originate from the centrioles.
They are part of forming the centrosome gamma tubulin ring complexes and the growing microtubules comprising the MTOC of animal cells
In which direction do microtubules (MTs) grow?
Minus to Plus end -towards periphery of cell - away from the centrosome.
What is the function of MAPs
microtubule associated proteins stabilize the plus ends and promotes polymerization and growth.
Result: longer, less dynamic microtubules
What does catastrophin (kinesin 13) do?
Promote destabilization of MT polymers - result in shorter, more dynamic MTs
What are the 3 classes of dynamic microtubules in mitotic spindles of animal cells?
- Kinetochore MT - attach each chromosome to the spindle pole
- interpolar microtubules - hold the two halves of the spindle together
- astral MT - interact with the cell cortex - act like an anchor
What is the function and structure of condensin?
- 5 subunit protein complexes (Smc2, Smc 4, Cap-G, Cap-H, Cap-D2
- catalyzes restructuring and compaction of chromosome DNA.
- Hydrolyzes ATP to coil DNA
What is the function and structure of cohesion?
- 4 subunit protein complex (Smc1, Smc3, Scc1, Scc3) with ATPase domain at one end
- Form ring structure and may encircle sister chromatids which are compacted around histones
What DNA repeat sequence is found at human centromeres?
What is usually flanking these repeats?
A-T repeats
Surrounded by pericentric hterochromatin
Describe the DNA organization of the chromatin that forms the centromere of human chromosomes
- H3 histone is substituted for CENP-A histone at kinetochore binding site.
- Chromatin with normal H3 is dimethylated at lysine 4
How many proteins are found in the kinetochore?
At least 12
What is the function of ATM/ATR? How and when are they activated?
Kinases which activate p53.
Activated through DNA damage before entering M-phase
What are Chk1/2 kinases?
Kinases which inactivate the M-Cdc25 phosphatase…prevents Cdc25 from removing inhibitory phosphate on M-Cdk.
What happens if DNA damage is extensive and p53 is highly expressed?
mitotic catastrophe (apoptosis)
What is the function of the APC
(APC) -anaphase promoting complex - leads to sister-chromatid separation in dividing cells
(Functions as an E3-Ubiquitin Ligase)
What is the function of securin?
Holds separase protein in an inactive conformation
What does Separase protein do?
When active, separate cleaves associated cohesin complex by cleaving Scc1 subunit. This allows sister chromatids to separate.
True or False: CDK inactivation in anaphase promotes separase activation by allowing its dephosphorylation?
TRUE: M phase cyclin degradation inactivates M-Cdk1 complex allowing separase activation because of NO phosphorylation
Describe the process of which CDC20 and APC promote sister chromatid separation
An inactive APC by CDC20 binding leads to ubiquination and destruction of securin. Destruction of securin allows separase to become active and cleave cohesins to allow sister chromatids to separate
What is the function of M phase cyclins
Activates M-CDK1.
Allows phosphorylation of separase - inhibits sister chromatid separation
What happens when kinetochores are all attached to MTs?
CDC 20 is activated and binds to APC complex to promote degradation of securin
How many chromatids are present that need to have their kinetochores attached to microtubules?
46 chromosomes -> 92 chromatids need to be attached
What is the “wait signal”
Period that ensures all kinetochores are attached to microtubules.
Single inhibitory signal given by unattached kinetochore is sensed and deciphered
What are the proteins that would override anaphase wait and create an “abnormal go” signal that leads to forced cell division?
Increase in: -Aurora kinases -Survivin -CDC20 Decrease in: -BubR2 kinase
What will happen to a cell that is left in the “no go” stage or is left paused for a long time?
Taxol promoted (apoptosis inducing drug) Mitotic catastrophe & apoptosis
What is the function of the Mad2 complex?
Mad2 binds to unattached kinetochores and sequesters/inactivates CDC20.
This prevents the CDC20 from binding to APC and causing progression of cell cycle
What will happen with an “abnormal go” signal?
- Polyploidy
- Genetic instability
