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The mammalian cell cycle: the autonomous stage and cell cycle targets in cancer therapy

Part 2 of 2
Published on March 30, 2023   21 min

A selection of talks on Oncology

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0:04
We talked a lot about the role of the CDKs in G1 phase or the cell responsive phase, how they interpret the extracellular signals and help drive the cell into the S phase, into the autonomous phase. But the cyclin CDKs are also involved in the cell autonomous phase. They are the hammers that will stop the cell cycle in response to the DNA damage errors or the mitotic errors.
0:29
We know that just to review the pre-replication complexes, assembled in G1, that means all the proteins that will sit on the origins of replication in our DNA waiting for that signal to start replicating. And that signal is really the cyclin E, cyclin A, CDK2-dependent signaling. They actually will phosphorylate members of the pre ARC complex, allowing that replication to begin, elongation will happen and then as we get to M-phase when we're starting to replicate the cell to undergo cytokinesis that also requires CDK activity. The CDKs are really integral in catalyzing the sequential activation of all of the steps from S-phase through M-phase.
1:18
Here's an example of this. You probably remember from your earlier biology classes, the mitosis phase, we start from an interface style which has disordered DNA in the nuclear membrane and then we have the different phases of mitosis, from prophase all the way to telophase. In prophase, the chromosomes start getting condensed so that they will not get broken during mitosis, then during metaphase, they're going to get separated and lined up on the metaphase plate so that as the cell and telophase undergoes that separation, pulling the chromatids to either side of the cell, getting ready for the closing off of these two new birthing, these two new daughter cells. CDKs trigger all the steps in this process. They trigger chromosomal condensation, they trigger nuclear envelope disassembly, so that the mitotic spindle can actually get to the chromatids and they trigger the assembly of the mitotic spindle itself. Conversely, they also trigger all of the steps that finish this process, so the chromosome decondensation as the chromosomes fall out of that chromatid state, the nuclear envelope has to be reassembled, and then the spindle has to be disassembled and cell-cycle signals in a stepwise fashion, catalyzing each of these steps. Their importance is emphasized as we move through the cell cycle.
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The mammalian cell cycle: the autonomous stage and cell cycle targets in cancer therapy

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