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Lecture 18

Lecture #18

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Jennifer Harris

Tuesday, March 17, 2009 - If we go back to the question he raised in the first lecture: How do cells control their shapes, their interactions, their numbers to build tissues, organs & organisms? - So far we re talked ab o ut co ntrol of cel l shape, cel l intera ct io ns wi th themselves or with the matrix & now hed like to turn to the control of cell numbers, both by controlling cell division & cell death & next week well talk more about mitosis & also the link to cancer b/c one of the key things to cancer is the control of cell number. - Next week well discuss more about cancer, but during the lecture today, hell also highlight molecules, link to the cell cycle that are also implicated in cancer as well & so well cover that again next week in more detail. Cell duplicates and segregates its genome - Here is the eucaryotic cell cycle illustrated in a basic way. Here we start off with a single cell and then that cell divides. A key aspect of this is that the material in the cell has to duplicate itself. If the cell is going to divide, a lot of material has to be produced so the cell cycle is important to have cell growth which is illustrated in this simple cartoon. You can see the increased size of this cell, so thats the increased growth of membranes, increased growth of the cytoskeleton, for example, mitochondria, ER membranes, Golgi membranes so theres enough material to divide into 2 for the next round. - The duplication and the segregation of the genome is critical because this encodes all the instructions for everything thats happening inside the cell so if there is a mistake made in the duplication of this genome, during the synthesis of the DNA, that could create mutations which would lead to problems in the cell. If during mitosis, certain chromosomes were lost, then of course thats going to cause problems as well. So its critical for both cells that are dividing & developing organisms that they synthesize & segregate their DNA properly during division so that those cells maintain a proper cell physiology & if they dont, then thats often associated with the development of cancers in our bodies. - Also for the proper passage of DNA from one generation to the another to maintain the species, they need to maintain their DNA properly to be able to pass on from generation to generation & this all comes down to the cell cycle & the control of how the cell duplicates & segregates the genome properly. - Here is the cell cycle in more detail, broken into specific phases. So we can start right here this is just after division has happened so this single cell has just been born from a division & the first phase is called G1 or gap phase 1 and it is a period of cell growth. Here is when the cell is partially doubling its proteins & organelles so that it builds up in size getting ready for a future division itself. So here its growing. - The next phase is called S phase which is dedicated to the synthesis of DNA so the replication of the genome. Here we have the replication of the DNA. - This is then followed by a second gap phase, G2, and this is another period of cell growth where the remaining proteins and organelles will duplicate themselves. - Then if everything is in order the cell will then enter M phase where both the nucleus & the entire cell will divide so 1 st yo ul l have a nucle r division, then youll have a cell division to split all the material of the cell in 2. - So next week well talk about mitosis in much more detail. Today were going to talk about the transition b/w these different phases. - You can see from the fact that it has 1 phase after the other, this needs to be temporally regulated & coordinated & there are many processes going on. - So a key thing for this is the cell must ask itself, it must check whether things are going okay during the process. Ex: Are there enough resources for DNA replication? Is this initial growth phase going effectively? Are there enough resources there for me, the cell, to replicate my DNA? Then for example, has the DNA actually replicated before mitosis starts? So before you start trying to split the DNA into two cells, the cell has to be sure it has actually replicated the DNA, that it has 2 copies of the DNA to separate into the 2 cells if it doesnt, then one of the cells is going to be missing huge sections of the genome. So these questions are asked at specific phases of the cell cycle. - So if we start again at this growth phase, before the cell goes into the S phase, the cell will ask itself is the environment favourable? Are there enough resources present? Here is a key checkpoint right here, the transition into the synthesis phase of the DNA so if there arent enough resources present at that time, the cell will just stay in G1 phase, it will wait until resources are available & then it will replicate its DNA when the conditions are better. - The other key point where there is a checkpoint is here for the entry of mitosis. Here it will ask is all the DNA replicated? Are there 2 copies of the genome to divide b/w the cells & it can also check again if the environment is still favourable. Here is a growth phase right here, the cell can monitor whether its growing properly, are there enough resources there? If there arent then it can halt again at this stage & wait until the environment is more favourable & then divide. - Then there are other checkpoints during mitosis & well touch on those again next week. Protein kinases - So the core molecules here are Cdks which are protein kinases & Cdks stand for cyclin dependent kinase. These are protein kinases & they have targets that control the cell cycle so they phosphorylate proteins that will control different stages of the cell cycle. - One key step is that another protein called a cyclin has to bind to these kinases to turn them on, so this is one way to turn on these molecules to pass through the checkpoint. - Diagram; Weve got the cyclin present here, here is the Cdk you need both of these components, and more as well see in a moment, to activate the checkpoint. At different stages of the cell cycle - So to co ordinate thin gs in time durin g this cycle, there are dif ferent cyclin-Cdk checkpoints at different stages of the cell cycle. - So if we started off here at G1 right here, the cell is growing, things are favourable, there are lots of resources available, if thats the case the cell will then signal to produce this S cyclin, the cyclin that will promote the synthesis phase. This will then bind to the S-Cdk & this complex can then phosphorylate machinery involved with DNA replication in the cell so the cell can dedicate all of its machinery to replicating the DNA. - Once that job is done, the cell wants to turn off that machinery since the genome has been replicated, they dont n
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