Regulation of DNA Replication
Replication, as we know means to replicate or duplicate. Therefore, DNA replication means to make copy of DNA molecule so as to maintain the continuity of the living organism. DNA replication is a very important process in any living beings.
DNA replication is important and different enzymes and steps are involved that assist in accurate completion of this process. Still, it is not necessary that this accuracy will completely prevent DNA from different physical or chemical agents that can damage it. Likewise, DNA replication is important during the time of cell cycle, at this period chromosomal DNA need to make its copy so that each daughter cell receive particular copy of the DNA molecule. Here also, it is important to maintain accuracy of replication because DNA contain genetic informations and any mistake or damage in the process of replication can lead to different disease in the offspring.
Therefore, in order to maintain the complete accuracy in DNA replication during cell cycle, scientist have found out the presence of different checkpoints that are present at different places to check every steps after their completion, and then make it move further. These checkpoints that are present in every step are regulated by different proteins. The main function of this checkpoints are to arrest the cycle if any error is found in replication cycle and then send the DNA for repair mechanism, so as to maintain the accuracy. How DNA replication is checked by these checkpoints is the main question of this topic? Now, we will look upon the several proteins that help to look for the error and repair it on time to carry on the replication process.
Firstly, before the beginning of replication pre- replication complex is formed that is guided by different proteins in different species. This complex ensures that DNA replicates only once in one cycle and origin activation. This process takes place at the early G1 phase of the cell cycle, when the activity of CDK is low and that of APC is high. In case of animals, APC helps to degrade any hurdle in cell cycle progression by destroying it, whereas in case of yeast CDK related proteins helps in either the export or degradation of any of such hurdles. Once, the pre- initiation complex is accurately formed and progressed, then different proteins get involved to activate the origin of replication. This process depends on the formation of pre- initiation complex that is formed in S phase. The formation of this complex is regulated by different checkpoints of s- Cdk and protein kinase Cdc-7 that restricts the origin firing under normal condition. Different types of protein under this families work to regulate the formation of pre- initiation complex.
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Secondly, as we know that during the replication process, strands of DNA gets separated forming the replication fork. So it is important to that this replication fork remains intact, i.e. there must not be breakage in the strand and in case any breakage is detected, the information is immediately send to the signal transduction pathway in order to make it confirm that the copy of DNA that has been passed to the offspring is accurate. Beside this, different protein kinase also helps to check the process of replication. The protein kinase named ATR/ATM arrest the cell cycle when any damage in the fork is encountered. This is done by phosphorylating Chk1 and Chk2. This phosphorylation in turns inactivates CDK1 and cdc25. This way cell cycle gets arrested until the damage in the fork is impaired.
After this step, it is generally noticed that the replication fork slows down at one or the other point, now why this happen is an important question here? The slowdown of replication fork is due to the breakage or lesions that are encountered during the process of DNA replication. Therefore, the more the damage is encountered more the time fork will take to complete the process of DNA replication.
Overall, regulation of DNA replication is effectively done during cell cycle by the presence of different proteins that guard to complete the replication process successfully.