Mitosis and Meiosis #16 Flashcards
Learning Objectives
- Describe structural and functional attributes of the mitotic spindle
- Explain key evens in various phases of cell division with an emphasis on cytoskeletal dynamics
- Describe the mechanisms of anaphase
- Compare and contrast key differences between mitosis and meiosis
In somatic cells, cell cycle divided into
Interphase (cell growth)
Cell Division
Interphase consists of:
G1, S, G2 stages of cell cycle
DNA replication occurs during S phase
What is a mitotic spindle
specialized arrangement of microtubules and associated motors that are essential for cell division in somatic cells
What are stages of Mitosis (5)
Prophase, prometaphase, Metaphase, Anaphase, Telophase
What happens to MT when mitotic spindle is organized
dramatic reorganization of cell’s MT
used to separate the replicated chromosome
What is cytokinesis
division of cystoplasmic contents that overlaps somewhat with nuclear division
Begins late anaphase and continues through telophase
Actin-myosin system invovled in cytokinesis
When does mitotic spindle BEGIN to form
during early prophase (in cytoplasm)
What is main component of mitotic spindle?
Microtubules
Many different MAPS (kinesin-related proteins and dyneins) and other regulatory proteins are present
IS Mitosis dependent on DYNAMIC properties of MTs?
What are antimitotic drugs?
YES! The ability to polymerize and depolymerize as wella s their ability to bind motor proteins is important
Drugs (colchicine-destabilizier; taxol-stabilizier) or conditions (cold, calcium) whcih affect MT stability , blocks mitosis
Drugs that either stabilize or destabilize MT structure and affect its funciton –> also affect mitosis
What does Cochicine do to MTs?
Depolymerizing agent
What does Taxol do?
Stabilizing agent for MTs
What are vinblastine and vincristine?
tubulin-sequestering drugs (depolymerize?)
Do these drugs only specify to mitotic spindles of cancer cells?
no. they also interfere with mitotic spindles of healthy cells as well as MT in non-dividng cells like neurons
side effects of chemotherapy with these drugs - GI isseus and neuropathy
What happens when there is abnormal spindle fucntion?
cells with genetic abnormalities are produced
duaghter cells can have missing or extra chrocomosmes
When does duplication of CENTROSOME occur?
Initiates during INTERPHASE as two halves of centriole separate and each serve as templaes for forming another half
What do new centrosome mature as
Mature as pericentriolar material enriched in gamma tubulin ring complexes
Centrosomal complex and do not begin to move to opposite poles of cell until prophase is initiated
As they move to opposite pole,s what to replicated centrosomes act as?
organizing regions for each half spindle
what happens when centrioles are duplicated?
They remain together in a large complex
Are centriole halves identical? How?
no!
The “mother” centriole is lager and more complex
Only mother centriole is ass. with pericentriolar matrix that nucleates MTs
Which centriole is assocaited with pericentriolar matrix that nucleates MTs
Mother Centriole
Are abnormalities in centrosome number, size, or shape common in many tumor cells?
YES
What do Centrosomal Defects result in?
- Spindle Abnormalities
- Chromosome missegregation and aneuploidy
- Hallmark of tumors
- Because interphase centrosome nucleate and organizes the microtubule cytoskeleton, centrosome abnormalieis could also contribute to disruption in teh overall cellular architercture of tumor cells
What is it beleived that aneuploidy is repsonsible for? (unbalanced completment of chromosomes?)
Could produce imbalance between growth-promotoing oncogenes and grwoth-regulating tumor suppressor genes –> lead to cancer
What are three types of MTs in fully formed mitotic spindle?
- Interpolar MT
- Kinetochore MT
- Astral MT
What are Interpolar MT
Extend form 2 poles of spindle towards equator
Most numberous f MTs
Overlap with polar fibers from other pole which have opposite polarity (mirror image)
What are kinetochore MT?
Attached to kinetochore structure of chromatids and extend towards spindle poles
What are Astral MT
radiate out from spindle poles towards cell membrane
Polariities of each half spindle is the same
Where is +/- for each MT type in spindle
- Plus end (fast growing end) is DISTAL from its spindle pole
Centrosome at spindle pole is ass. wth minus end of MT
Kitetochore and polar MTs, the + end is nearest the equator
Astral MT, + end is closest to cell membrane
What is a key step during prophase for spindle formation
Why?
Breakdown of nuclear evelope (late prophase, or prometaphase)
many of the motor proteins and MT regulators that promote spindle assebmly and function are in the nucleus
What is invovled in chromosome condensing during prophase?
Protein kinase
what triggers nuclear membrane breakdown in late prophase (prometapahse)
phosphorylation of elements in teh nuclear pore complex and nuclear lamina
kinetochore MT begin to form, stiumualte dby local environemnt of chromcosomes, and begin to capture chromatids
Dramatic changes in MT stability during early mitosis how?
1/2 life of avg MT decrease by 20x as cell enters prophase and may cytoplasmic MT disappear
This provides tubulin subunits to build spindle apparatus and enable rapid MT turnover
hat proteins are invovled with destabilizing MT arasys?
Catastrophic factors increase catastrophes
MAPS are invovled with increasing frequency of rescues
How does spindle self organize by MT motors
Nucleation
Antiparallel cross linking by kinesin
Outward push by kinesin
Focus of poles by dynein and kinesin
pushing, pulling, slididng, tugging until poles are properly positiioned
What is cytosolic dynein involved in?
expt?
Formation and stabilization of mitotic spindle poles
Cytosolic dynein-minus end directed motors is involved in consolidating normal FOOTBALL LIKE shape of spindle
Expt: blocked bytosolic dynein –> abbrantly formed spindle
where are kintetochore MT attached?
Centromere that bind sister chromatids together
Where are kinetochore + ends?
proximity to kinetochore!
What DNA controls genetration of a kinetochore?
CEN DNA (centromeric DNA) which rectruites and binds various proteins that make inner layer of kinetochore
What way of growth of kinetochore MT?
while plus end appears to be capped in kinetocohore, remains active MT end that undergoes assebmly/disassembly reactions
How are chromosmes “captured” by MT?
Highly dynamic MT in late prophase probe , search, and capture
gorwign and shrinking + ends –> allows some MTs to grap or capture a kinetochore
MOre often, kinetocore encounters MT side wall rather than teh end–> motor proteins slide kinetochore to + end of MT –> captures MT
When both kiethcores properly attached, fibers are stabilitzed
Describe balance of forces in metaphase spindle
Opposing forces (pusha nd pull) align chromosome on equatorial plate as cell approaches metaphase
What is polar ejection force?
acts on chromosome arm that is severed from its kinetochore and quicly moves away form pole (push) while other half with kinetochore is pulled
What is a spindle assembly checkpoint?
only after ALLLL kinetochores are captured and chromosomes are aligned on equator will cell intitate anaphase
When does dell intiate anaphase?
only AFTER ALL kinetochore captured
What happens during anaphase gnerally?
shortest part
chromosomes seaprate and move to poles
What happens at telophase general
reformation of nuclear enveoleme
decondensation of chrocosomes
Chromatid separation triggers anapahase
Anaphase entry-the separation of chromatid
very start of anaphase, sister chromatidds break apart
cohesin complexes taht connect chromatids along lenght are cleaved after degradation of an inhibitor to a protease which targets cohesin occurs
ca
What are the two stages of Anaphase?
Anapahse A (early)
Anaphase B (alte)
show differential sensitivity to various drugs and inhibitors–suggesting that different mechanisms are involved in each phase
What happens during anaphase A?
during which chromatids move towards teh pole and kinetochore MT shorten
movement of daughter chromosomes to poles
forces generated mainly at kinetochore
What happens during anaphase B?
spindle elongates and poles of spindle move further apart
- sliding force is generated b/w interpolar microtubules from opposite poles to push poles apart
INterpolar MT elongate
- pulling F acts directly on poles to move them apart
Mechanisms of anaphase A involve active MT disassembly
Evidence suggests that motor proteins are NOT directly involved since this step has been documeted in teh absence of ATP
Anaphase B requires 3 processess: What are they?
- Pushing Force
- Pulling force (all of which require energy and
- net assebmely which increases MT length
Does Anaphase B require ATP?
yes, requires motor proteins at pole
What else happens during Anaphase B?
regions of microtuble overlap at midzone becomes shorter –> antibparallel polar MTs from oppsote poles slide relative to each otehr
Interpolar MTs get loner,
Cytosolic dynein, minus-end directed motor protein involved in moving poles further apart
Kinesin-relsted proteins
KRPS appear to be involved
Describe what occurs during cytokinesis
Nuclear and Cytoplasmic (cytokinesis) are separate events
In vertebrates, mitotic spindle poles (centrosomes) play essential role in determining positionging and timing of cytokinesis
When does cytokinesis begin?
anaphase and contineus through telophase and into interphase
What kind of cytoskeleton does cytokinesis use?
Actin/myosin II interactions
