Cell Division Flashcards
relatively how much shorter are chromosomes than linear DNA itself?
About 10000X, so you need an F ton of packaging
T/F. Sister chromatids are genetically identical and share a centromere.
False, they are genetically identical but they do not share a centromere
what is a centrosome
organelle, microtubule protein organizing center
T/F. Physical position of centromere matters.
False, it can be near the end, or middle of chromosomes and configurations work just fine
how can we ID centromere DNA sequence?
budding yeast experiments, asymmetric division. ID’d 125bp centromere sequence necessary and sufficient to confer centrosome identity
neocentromeres
acquisition of a new centromere at a new chromosomal site. people with this issue typically asymptomatic, with the exception of fertility issues due to problems with meiosis
if DNA sequence is not sufficient for centrosome recognition, what is?
Histone marker CENP-A is the conserved epigenetic mark that specifies centromere identity. CENP-A has a divergent N-terminal tail from H3, and the DNA is slightly underwound at entry and exit point in the chromosome. This ID’s a unique epigenetic environment, stabling inherited over generations, that affects where centrosomes form.
what do kinetochores do?
- can drive chromosome movement through — mitotic assembly checkpoint
- assemble on centromeres and link chromosomes to microtubule plus ends
how many microtubules can each kinetochore bind?
about 20, called a kinetochore fiber
what are two varieties of microtubules
astral and polar
what does kinesin do?
kinesin walks along polar microtubules to conteract forces that would otherwise collapse the spindle
how is dynamic instability of microtubules maintained?
ends always GTP bound, but this GTP is rapidly hydrolyzed, causing the end to kink a little bit - makes protofilaments want to start to peel apart. You resist this conformational strain by having a GTP bound cap.
T/F. it’s much easier to extend an existing filament than to start a new one
True. Gamma tubulin ring complex nucleate microtubules, become a platform for the building of new microtubules.
explain the “search and capture” hypothesis of microtubule/kinetochore interaction
- centrosome is major microtubule organizing center in animal cells. centrosome can probe space around it by shooting out MTs that are rapidly growing a shrinking stochastically. When they grow and hit a kinetochore, they form a stable complex that initiates shit. “search and capture hypothesis”. if two cells enter into mitosis at the same time, they can complete division at diff times due to this stochastic MT capture process
how can a kinetochore remain bound to a microtubule while being actively depolymerized?
This is an ongoing area of research, but likely due to motor molecules at kinetochore capable of tracking depolymerization
How many times is the centrosome duplicated per cell cycle?
Once
What happens if you have too many centrosomes
multipolar spindles and poor division
what do interpolar microtubules between chromosomes
do?
help maintain shape
how do cells identify replication products and maintain their identity?
sister chromatid cohesion. release of cohesive glue during metaphase and anaphase transition allows for their faithful separation.
why is sister chromatid cohesion important?
It has allowed for the evolution of large, segmented, complex genomes and surveillance mechanisms to ensure fidelity, mechanism for DNA repair
How to ID proteins required to hold sister chromatids together?
GFP/LacI repressor screen in a lacO array, visualized by formation of 2 GFP loci. Looked for mutants arrested in metaphase, with two dots
how do you get out of mitosis?
Cdk1
Sister chromatid disjunction and mitotic exit are independant, separate events. So what holds it together?
APC/C (anaphase promoting complex) - huge 13 subunit complex that ubiquitinates two key substrates in mitosis: cyclin B1 and securin
- securin destruction initiates anaphase - bound stoichiometrically to separase, a protease responsible for cleaving cohesin
T/F. Traditionally defined cell cycle checkpoints are essential
False, they’re all supposed to be nonessential, though the mitotic checkpoint is required for every cell division and is called a checkpoint
How can kinetochores mess up? (3)
- If only one kinetochore is attached but not both - in this case MCC released.
- Another type is syntellic, which both sister chromatids attached at same pole. If mitosis proceeds both sister chromatids will go into same cell upon division. tension required to stabilize attachment.
- another type of attachment is merotelic, where you have MTs binding to either/both chromatids, can’t be detected by cells. Accumulate at high frequency in human cancer cells.
How does tension stabilize microtubule attachment?
by spatially separating substrates
what are two key differences in meiosis vs mitosis regarding kinetochores/division?
coorientation of sister kinetochores, then cohesion is removed in 2 distinct steps
Aneuploidies are responsible for most spontaneous abortions. why does this get more common the older women get?
current hypothesis - “cohesion fatigue”. steady decline of cohesion ring complexes, means embryo has aneuploidy and is aborted
what are the layers of chromatin compaction?
linear DNA, beads on string histones, “30nm fibers” (controversy, but still), radial loops, heterochromatin, metaphase chromosome
how does cohesin ring bind chromatids together?
it’s a tripartite ring structure that topologically embraces the DNA duplex - at least that’s the model
