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Lec 24 The Cell Cycle Control.docx

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BIOL 1010
Igor Kovalchuk

The Cell Cycle Control Lecture 24 “To divide or not divide, that is the question” Summary - The role of cell division- reproduction and growth (cell renewal and repair) - The mitotic cycle- consists of: o Interphase (I=G 1S+G )2 important steps for DNA duplication and initiation of mitosis o Mitosis (P+PM+M+A+T) – separation of two daughter cells with equal amount of genetic material (chromosomes) The cell cycle control - The timing and rate of cell division differ between different organisms and also between different cells of an organism o Compare skin cells with muscle or nerve cells - What is controlling the rate of cell division, how cells “know” that it is time to divide - Why cancer cells do not stop dividing? The cell cycle - Experimental evidences suggested that the cell cycle is driven by specific chemical signals present in the cytoplasm - Most of the experiments were conducted with cell cultures - Many types of animal and plant cells can be removed from an organism and cultured in an artificial environment - Cultured mammalian cells can be induced to fuse, forming a single cell with two nuclei - The results of fusing cells at two different phases of the cell cycle suggested that particular chemicals control the progression of phases. o For example, when a cell in M phase was fused with one in any other phase, the nucleus from the latter cell immediately began mitosis o If the second cell was in G1, the condensed chromosomes that appeared had single chromatids. The cell cycle control system - These experiments suggested that evens happening from one cell division to another are driven by cell-cycle control system. - A cyclically operating set of molecules in the cell that triggers and coordinates key events in the cell cycle - When and how is the cell cycle controlled? Cell cycle is controlled! - G 1ucleus is competent to replicate S-phase cells contain activator - G 2uclei aren’t competent and do not re-replicate. G cells do2not inhibit replication. S-phase nuclei retard mitosis in G n2clei - G 2ells do not suppress S-phase entry of G - phas1 nuclei Cell cycle control - A checkpoint in the cell is critical control point where stop and go signals can regulate the cycle - Animal’s cell shave built in “stop” signals that halt the cell cycle at checkpoints until overridden by “go” signals. - To function properly checkpoint signals have to percept “repots: from crucial cellular processes: o Have it been completed correctly and should the cell cycle proceed o Checkpoint also register signal from outside the cell. - The most important decisions to make are: to continue the cell division after the exit from M phase or not. - Cell that do not receive the “go” signal at the G che1kpoint switch into a non-dividing state called the G phase 0 o A good example of quiescent cells are liver cells. o They can be called back to the cell cycle by growth factors released during injury Cyclins and cyclin-dependant kinases (Cdks) - Regulatory molecules of the cycle transition are proteins of two main types: protein kinases and cyclins - Protein kinases are proteins that regulate the activity of the others by phosphorylating them - “Go” signal at the G an1 G chec2points is regulated by particular protein kinases - To be active, such a kinase must be attached to a cyclin, a protein that gets its name from its cyclically flucating concentration in the cell - The Kinases are called cyclin-dependent kinases- Cdks Control at the G ch2ckpoint - The stepwi
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