BIOL2200 Lecture Notes - Lecture 7: Ultimate Tensile Strength, Desmin, Epidermolysis Bullosa Simplex
CYTOSKELETON LEC 4 BIOL2200
LEC 4
Mitosis: a special case of microtubule regulation
Microtubule undergo a massive restructuring during mitosis
The mitotic spindle appears - specialised structure for the separating chromatids
Microtubules changes during mitosis
oCells duplicate their centrosomes prior to cell division (just before prophase)
oMany cancer cells have more than one pair of centrosomes, thought to contribute to
genetic instability and aneuploidy
Spindle movement
oSpindle microtubules bind to the kinetochore
oChromosomes need to the line up along the midpoint, then get pulled apart
oThis is achieved by a combination of sliding (kinesin, dynein) and treadmilling
oThe astral microtubules anchor the cell cortex and pull on the centromeres
End result: two daughter cells
The cytoskeleton as a target for anti-cancer treatment
Vinblastine
Plant alkaloid, originally from the Madagascan periwinkle
Chemotherapy for a variety of cancers including Hodgkin's disease, non-
Hodgkin's lymphoma, testicular, breast, lung, head and neck, and bladder cancers,
and Kaposi's sarcoma
Major side effects include low blood counts due to bone marrow
suppression. White and red blood cells and platelets may temporarily decrease
Often combined with other chemotherapies such as bleomycin and
methotrexate as it allows lower doses of the latter two to be used
Mode of action of vinblastine
Binds to beta-tubulin subunits at + end, inhibiting further polymerisation of
microtubules
Causes M phase specific cell cycle arrest by disrupting microtubule assembly
and proper formation of the mitotic spindle and the kinetochore
Therefore vinblastine inhibits microtubule assemble
Paclitaxel (Taxol)
Treatment of ovarian, breast and lung, bladder, prostate, melanoma,
oesophageal, and other types of solid tumour cancers as well as Kaposi's sarcoma
First isolated from the Pacific Yew Taxus brevifolia (hence its first name,
taxol)
Now synthesised
Mechanism of action of pacitaxel
Like vinblastine, binds to beta-tubulin
However unlike vinblastine, paclitaxel binds to a different site on the beta-
tubulin monomer and this results in stabilisation of microtubules
This blocks metaphase spindle formation
Effect of vinblastine and paclitaxel on mitosis
Normal cell cycle, no drug
Drug treatment results in spindle pole abnormal
Intermediate filaments another network of filaments that radiates from the nucleus
10nm diameter filaments
find more resources at oneclass.com
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Document Summary
Microtubule undergo a massive restructuring during mitosis. The mitotic spindle appears - specialised structure for the separating chromatids. Cells duplicate their centrosomes prior to cell division (just before prophase: many cancer cells have more than one pair of centrosomes, thought to contribute to genetic instability and aneuploidy. Chromosomes need to the line up along the midpoint, then get pulled apart. This is achieved by a combination of sliding (kinesin, dynein) and treadmilling. The astral microtubules anchor the cell cortex and pull on the centromeres. The cytoskeleton as a target for anti-cancer treatment. Chemotherapy for a variety of cancers including hodgkin"s disease, non- Hodgkin"s lymphoma, testicular, breast, lung, head and neck, and bladder cancers, and kaposi"s sarcoma. Major side effects include low blood counts due to bone marrow suppression. White and red blood cells and platelets may temporarily decrease. Often combined with other chemotherapies such as bleomycin and methotrexate as it allows lower doses of the latter two to be used.
