Task Answers
Topic 1, Key Area 5
Task 71
Make your own notes about the role of the cytoskeleton and the key protein molecules that form the cytoskeleton.
The cytoskeleton is a 3D framework within the cytoplasm that provides mechanical structure and support to cells. It includes microfilaments (e.g. actin), intermediate filaments and microtubules. Together, these protein structures control the movement of organelles and chromosomes. They are responsible for the dynamic property of cell structure.
Task 72
State the three types of structures and sketch a diagram of a microtubule, labeling the protein it is composed of.
Cytoskeleton comprises microfilaments, intermediate filaments and microtubules. Microtubules are long, hollow tubes made from dimers of a globular protein called tubulin. They are dynamic structures and can grow by polymerisation of tubulin dimers, or breakdown and retract by depolymerisation.
Task 73
"Read through this article ("Microtubule polymerisation: one step at a time") and then we will watch this video" (accessed via the pink button).
You can now do the same. Use a highlighter (if printed) or add sections into your notes to show parts of the text that help you understanding what is meant by “polymerization of tubulin” during the cell cycle. How would you cite and reference the article using Harvard referencing system?
Some key pieces of information about "polymerisation":
Microtubules are made of tubulin dimers (alpha and beta) to form polar filaments.
Tubulin binds to GTP to polymerise. GTP hydrolysis is important for tubulin growth and stability.
Tubulin filaments may have a GTP cap some distance from either end to prevent curving of the structure and maintain stability.
Polymerisation involves additions of single tubulin subunits.
"Dynamic instability of microtubules" refers to the ability of these structures to undergo rapid cycles of growth and shrinkage. Alpha and beta tubulin are bound to GTP; GTP bind to beta tubulin is hydrolysed after addition.
Citation: (Sept, 2007)
Reference: Sept, D., (2007), Microtubule polymerisation: One step at a time. Current Biology, 17 (17), page R764-R766.
Task 74
Sketch a diagram of the cell cycle to show interphase and the mitotic phase .
Task 75
Describe the three stages of interphase.
Interphase comprises 3 stages, G1, S and G2. G1 and G2 are periods of cell growth and organelles are synthesised and the protein complement increases within the cell. S phase involves duplication of the genetic material in preparation for nuclear division during the Mitotic phase. Ultimately, interphase ensures the full cell and its contents are ready for division.
Task 76
During prophase, spindle fibres extend from the MTOC by polymerisation and attach to chromosomes via their kinetochores in the centromere region. Carry out some research and draw a labelled diagram to show all structures mentioned in this description.
Diagrams provided - one more professional than the other (left = more professional in case you were wondering...)
Starter Task
Before we begin, challenge yourself to complete this quick Retrieval Practice Quiz (1-4). Question 5 is an opportunity for you to dig deep and think. Grab a pen and paper and write your answers:
State the name of the cell cycle stage that includes G1, S and G2. INTERPHASE
Name the 4 stages of mitosis, in order. PROPHASE, METAPHASE, ANAPHASE, TELOPHASE (Pee on the MAT).
What happens during S phase? CHROMOSOMES ARE REPLICATED
What is the product of one round of the cell cycle? 2 GENETICALLY IDENTICAL DIPLOID DAUGHTER CELLS
Consider the control of the cell cycle - what do you think this might look like? How is tight regulation achieved? No clues from me here...you will have to read on! I wonder what you wrote though... :)
Task 77
Watch the video and answer the following questions:
How is the cell cycle controlled? IT IS TIGHTLY CONTROLLED BY A SERIES OF CHECKPOINTS
What triggers the start of the cell cycle? THE CELL RECEIVES AN EXTERNAL SIGNAL TO DIVIDE
What happens during S phase? THE DNA IS DUPLICATED/ REPLICATED.
What must be achieved before the cell cycle can enter M phase? IF THE INTRACELLULAR ENVIRONMENT IS "FAVOURABLE" AND THE DNA HAS BEEN DUPLICATED CORRECTLY, THE CELL WILL ENTER M PHASE. By favourable, this means that the cell has grown appropriately and synthesised organelles. This is detected by the concentration of proteins, particularly cyclins, which activate kinase enzymes.
Describe the functions of kinases during M Checkpoint. CAN FUNCTION TO ENSURE THE CHROMOSOMES ARE CORRECTLY ALIGNED TO THE MITOTIC SPINDLE.
Why are some of these kinases targets for drug development in cancer therapeutics? THESE KINASES ARE PROTO-ONCOGENES ARE, IF MUTATED, BECOME ONCOGENES THAT PROMOTE TUMOUR FORMATION. DEREGULATION OF CHECKPOINTS DURING CHECKPOINT MIGHT BE A TRIGGER FOR CANCER DEVELOPMENT - THIS COULD BE CAUSED BY KINASE MALFUNCTION. MANY KINASES ARE OVEREXPRESSED IN CANCERS.
Task 78
Explain what the graph shows and note any differences compared to the chart you've already seen.
The graph shows the changes in concentration of cyclin-dependent kinases during different stages of the cell cycle; this mirrors what was seen in the previous graph looking at the concentration of cyclins. We know that, as the cell grows and synthesises organelles, proteins are produced, including cyclins. These cyclins accumulate and bind to cyclin-dependent kinases. Once a cyclin-CDK complex has been formed, the CDK is activated and begins phosphorylating target proteins. Threshold levels of phosphorylation are reached and trigger passage of the cell cycle into the next phase.
By comparing the two graphs on the page, we can see the cyclin E peaks in concentration during G1. This must bind to and activate G1-CDKs. Cyclin D accumulates and reaches a peak during S phase, activating S-phase CDKs.
Task 79
Control of the cell cycle involves the activation of cyclin-dependent kinases that catalyse phosphorylation of target proteins. One such target, during G1, is retinoblastoma. In your own words, describe the consequences of phosphorylation of retinoblastoma with respect to cell cycle progression.
During G1 of interphase, cyclin proteins accumulate (cyclin E based on the graph shown earlier) and bind to and activate G1-CDKs. These go on to phosphorylate target proteins, including retinoblastoma (Rb). Rb is usually, in the dephosphorylated state, bound to a transcription factor; in this conformation, the transcription factor cannot bind to and promote gene transcription. However, following phosphorylation of Rb, the conformation of Rb changes and releases the transcription factor. This can then bind to the promoter region of genes, resulting in their transcription. These genes are required for progression into S phase.
Starter Task
Retinoblastoma is phosphorylated during G1 of the cell cycle. The answer to this question is A.
Task 80
Reflect on the videos you've seen and the information you've gained to describe the process of apoptosis. What steps are involved? You might want to do some additional research at this point to gain a deeper understanding of this process.
Suggested answer - You do NOT need to know the details of this for your exam but useful to have a deeper understanding of the process.
Cells that die as a result of acute injury typically swell and burst. They spill their contents all over their neighbours - a process called cell necrosis - causing a potentially damaging inflammatory response. By contrast, a cell that undergoes apoptosis dies neatly, without damaging its neighbours. The cell shrinks and condenses. The cytoskeleton collapses, the nuclear envelope disassembles, and the nuclear DNA breaks up into fragments. Most importantly, the cell surface is altered, displaying properties that cause the dying cell to be rapidly phagocytosed, either by a neighbouring cell or by a macrophage, before any leakage of its contents occurs. This not only avoids the damaging consequences of cell necrosis but also allows the organic components of the dead cell to be recycled by the cell that ingests it (Alberts et al., 2002).
Image from Alberts et al. (2002).
The intracellular machinery responsible for apoptosis is similar in all animal cells. It depends on a family of proteases that have a cysteine at their active site and cleave target proteins at a specific asparate residue. They are therefore called caspases. Caspases are synthesised in the cell as inactive precursors, called procaspases, which are usually activated by cleavage at asparate residues by other caspases. Once activated, caspases cleave, and thereby activate, other procaspases, resulting in an amplifying proteolytic cascade. Some of the activated caspases then cleave other key proteins in the cell. Some cleave the nuclear lamins, for example, causing the irreversible breakdown of the nuclear lamina; another cleaves a protein that normally holds a DNA-degrading enzyme (a DNAse) in an inactive form, freeing the DNAse to cut up the DNA in the cell nucleus. In this way, the cell dismantles itself quickly and neatly, and its corpse is rapidly taken up and digested by another cell (Alberts et al., 2002).
Task 81
Watch the video ("What is apoptosis? University of Dundee) and then, using what you have learned so far, outline the similarities and differences between the intrinsic and extrinsic apoptosis pathways. Try and present this in a clear, concise way in your notes, e.g. a table or flowchart.
Plenary Task
Which of the following would NOT be a substrate for caspases?
Answer - A: DNA