DNA Damage Checkpoint is Rad!!!

How are cells able to replicate themselves so precisely, again and again? Going through each division cycle requires that the cell coordinate many complicated processes, and yet they manage to do it with extremely high accuracy and precision each time. But how does the cell make sure that everything happens in the correct order, and that any mistakes are corrected before going to the next step?

For example, how do cells ensure that DNA is accurately replicated before the cell goes through mitosis? In the 1980’s, Weinert and Hartwell reasoned there are two simple possibilities- first, successful mitosis could directly depend on having properly replicated chromosomes, rather like a car needing wheels in order to move. The other possibility is that the cell has a control system in place that halts the cell in S phase until it senses that the DNA is correctly replicated, similar to an inspector examining the car before it can leave the shop.

But how to distinguish between these two possibilities? The investigators looked specifically for mutant cells that did NOT arrest in response to radiation, indicating that this hypothetical control system was no longer functioning. These cells were missing their DNA damage checkpoint, and could no longer detect and repair damaged DNA- a critical step in ensuring faithful replication!

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