slide set 18 Flashcards
active Cdk1/cyclin B drives…
drastic changes in mitosis to segregate the replication genome and produce two daughter cells
As DNA is replicated in S phase, copies are held together with…
cohesion proteins
hold sister chromatids together in S phase to M phase
Errors in mitosis or meiosis
have profound consequences
several successful chemotherapies block mitosis
Taxol (paclitaxel)
Stabilizes microtubule filaments by binding along them and inhibits mitosis
Prophase
- replicated chromosomes condense (pack together tightly)
- mitotic spindle assembles between 2 centrosomes (outside the nucleus)
- 2 centrosomes have replicated and moved apart
nucleus and cytoplasm are still separate
In prophase, the chromosomes condense
- condensin protein complexes catalyze restructuring and compaction of chromosomal DNA
- condensin complexes resemble cohesion, which holds sister chromatids together
- It is not clear how it functions, but the complex is through to encase loops of DNA
replicated chromosome is made up of
2 closely associated sister chromatids
Prometaphase
- abrupt breakdown of nuclear envelope
- chromosomes can attach to spindle microtubules via their kinetochores and undergo active movement
there is no longer a distinction between nucleus and cytoplasm
mitotic spindle
2 centrosomes formed at opposite sides of the cell
composed of 2 spindle poles
Metaphase
Brief!
- chromosomes are aligned at equator of spindle, midway between spindle poles
- kinetochore microtubules attach sister chromatids to opposite poles of the spindle
Anaphase
- sister chromatids synchronously separate to form 2 daughter chromosomes
- each is pulled slowly toward the spindle pole it faces
- Kinetochore microtubules gets shorter, spindle poles move apart
Both processes contribute to chromosome segregation
Telophase
- 2 sets of daughter chromosomes arrive at poles of spindle and decondense
- New nuclear envelope reassembles around each set, completing formation of 2 nucleu and ending mitosis
- division of cytoplasm begins with contraction of contractile ring
- contractile ring: actin myosin ring is just under cell membrane
- starts to pinch cells together
contractile ring
contractile ring: actin myosin ring is just under cell membrane
starts to pinch cells together
Cytokinesis
- cytoplasm is divided in 2 by a contractile ring of actin and myosin filaments
- contractile ring pinches the cell in 2 to create 2 daughter cells, each with 1 nucleus
spindle structure at metaphase
sister chromatids are held together and connected to spindle poles on microtubules
centrosomes have gamma tubulin nucleating complexes
centrosome nucleates a lot of microtubules: plus ends face out
plus ends project away from spindle pole
minus ends anchored at spindle poles
different types of microtubules
differ in where they are and what they bind to
structure is always the same! (we learned this last exam)
Centrosomes
nucleate MTs
the minus MT ends are focused at the spindle pole
kinetochore
protein complex that links together microtubules and chromatid
Centrioles replicate in ___ phase.
centrioles replicate in S phase (at same time that DNA is replicated)
- As cell moves from S phase, through G2 and into M phase, the pericentriolar material (including gamma tubulin ring complexes) expands
- More gamma tubulin ring complexes at the centrosome lead to greater ability to nucleate microtubules
kinetochores are…
kinetochores are protein complexes that link the sister chromatids to microtubules
kinetochore structure
kinetochore layers are composed of many proteins
kinetochores attach to…
microtubule plus ends
- proteins extend out of the kinetochore that hold on to the plus ends of the microtubule
- there is a gap in space between the chromatid and microtubule, which are linked by the kinetochore
- end-on attachment: the microtubule end is attached to the kinetochore
MT dynamic instability
switches at mitotic entry to promote more rapid MT turnover
- MT are shorter during mitosis and more frequently switch between growing and shortening
- centrosomes mature and nucleate ~5x more MTs from each spindle pole
- These changes are driven by active Cdk1/cyclin B complexes phosphorylating target proteins
Cdk1/cyclinB (directly or indirectly) targets…
microtubule-associated proteins and motors
- Cdk1/cyclin B, when active, can phosphorylate target proteins to turn them on or off
- The net effect is a dramatic shift in microtubule dynamics during mitosis
Rapid MT dynamics from oppostie centrosomes allows:
MTs to connect to chromosomes
MT dynamic stability to search space
kinetochores capture dynamic MTs at plus ends and MTs become stable
(A) In late prophase of most animal cells, the mitotic spindle poles have moved to opposite sides of the nuclear envelope, with an array of overlapping microtubules between them. (B) Following nuclear envelope breakdown, the sister-chromatid pairs are exposed to the large number of dynamic plus ends of microtubules radiating from the spindle poles. In most cases, the kinetochores are first attached to the sides of these microtubules, while at the same time the arms of the chromosomes are pushed outward from the spindle interior, preventing the arms from blocking microtubule access to the kinetochores. (C) Eventually, the laterally-attached sister chromatids are arranged in a ring around the outside of the spindle. Most of the microtubules are concentrated in this ring, so that the spindle is relatively hollow inside. (D) Dynamic microtubule plus ends eventually encounter the kinetochores in an end-on orientation and are captured and stabilized. (E) Stable end-on attachment to both poles results in bi-orientation.
