Question 2 (1pt). A paper published in 2009 looked at a new chemotherapy drug ca
ID: 132030 • Letter: Q
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Question 2 (1pt). A paper published in 2009 looked at a new chemotherapy drug called In this paper they monitored microtubule length (y axis) over time (x axis) in untreated cells (top microtubule (4 per graph). The authors claim that carbendazim inhibits dynamic instability of graph) and carbendazim treated cells (bottom graph). Each line on the graph represents one microtubules. Do you believe them? a. First, explain what a GTP cap is on a microtubule and its effect on microtubule assembly/disassembly. assemblyldisassembly (0.125). A. untreated 025): Correct explanation of GTP cap (0.125) and effect on b. Graph A is the control for the experiment. The microtubule represented by the dark grey line (red arrow) seems to be steadily increasing in length over time. Describe what is happening on the plus end of the 3 B. + carbendazim microtubule with regard to addition of a/ß tubulin-GTP and GTP hydrolysis. Rubric (0.25): Correct statement about GTP hydrolysis at plus end (0.125). Correct statement about GTP addition at plus end (0.125) c. Graph A is the control in the experiment. The microtubule represented by the open circles (green arrow) seems to increase and then dramatically decrease in length over time. Describe what is happening on the plus end of the microtubule with Time (min) regard to addition of ? ? tubulin-GTP and GTP hydrolysis to cause this to occur. Rubriceaan Correct statement about GTP hydrolysis at plus end (0.125). Correct statement about GTP addition at plus end (0.125) d. Graph B shows the microtubule length over time in the presence of carbendazim. The mode of action for carbendazim is unknown, but it supposedly inhibits dynamic instability. First, explain the result you see in Graph B with regard to microtubule dynamics. Next, given what you know about microtubule dynamics, speculate on a plausible mechanism that would give you the result above. Rubric (0.25): Correct observation of effect on microtubule dynamics (more dynamic7, more stable7) 10.125) and logical mechanism by which carbendazim could cause this result (0.125).Explanation / Answer
The claim of authors that carbendazim inhibits dynamic instability in microtubules is correct
Answer a) A microtubule is composed of tubulin which itself is a dimer formed of two proteins ? - tubulin and ?-tubulin. Both these are globular in nature. The ends of microtubules are designated as (+), where only ? part of dimer is exposed and (-), where only ? part of dimer is exposed. The assembly and breakdown both occurs mostly at (+) end. Both the tubulins are associated with one molecule of GTP each, GTP cap is that region on microtubule's (+) end, where the hydrolysis of GTP to GDP has not occurred till now.
Effect of GTP cap: Once the GTP cap is removed, i.e. the hydrolysis of GTP takes place GDP-tubulin is formed which can curve and hence cause the disassembly of microtubule filaments.
Answer b) In graph A, the curve (dark grey) which is steadily increasing with time indicates that (+) end is undergoing elongation and tubulin dimers containing GTP are getting added to the microtubule and getting polymerized.
The hydrolysis of GTP to GDP is not taking place in the microtubule under consideration.
Answer c) In graph A, the curve which first increases in length and then decreases indicate that firstly polymerization is occurring at (+) end and so length is increasing and no hydrolysis is taking place.
When the length starts decreasing, the hydrolysis of GTP to GDP takes place and depolymerization i.e. removal of tubulin subunits is taking place at (+) end.
Answer d) Graph B indicates the effect of carbendazim on microtubule length. As observed from curves, no significant elongation of microtubule occurs over time in any case. So, carbendazim suppresses the instability and makes them less dynamic.
Mechanism: Carbendazim may have affected the instability of microtubules by preventing the GTP-bound tubulins to get attached to (+) end or causing the hydrolysis of GTP to GDP as soon as a dimer gets attached.
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