This is a general question about DNA replication. I have an exam coming up and m

Question

This is a general question about DNA replication. I have an exam coming up and my teacher has emphasized thinking about what would happen if the different enzymes in the process became mutated. For example, if DNA ligase was mutated, I would assume there would be a bunch of fragments, but I don't know for sure. Can someone direct me to a place where I can get concrete answers, or tell me what would happen?

Here are the enzymes that we have discussed: Ligase ,DNA Polymerase III, DNA Polymerase II, Single Stranded Binding proteins, Helicase, Primase, Girase

Thanks so much!

Explanation / Answer

DNA replication is a vital and complex phenomenon. A Number of enzymes and cellular mechanisms are involved in this. Moreover, all these enzymes are dependent on each other. An Activity of one enzyme regulates the function of other enzymes. It is practically difficult to state that what will happen when a single enzyme is mutated. Because it can affect on its own activity but also on subsequent consequences in replication and obviously further in transcription and translation. Still I have tried to compile major functions of these enzymes. If you want to study in detail the mutation effects of above enzymes, first study the enzyme structure and its mode of action in detail and then move toward the mutational effects.

DNA Polymerase

DNA polymerases are enzymes that are responsible for elongation of the newly synthesizing DNA strand. It can not initiate replication of its own. There are --- types of DNA polymerases and these are known for their specificity as well as for accuracy. The approximate rate of error is one/109 bp. DNA Polymearse II is an enzyme that is closely related to mismatch repair/ proofreading and acts mainly on lagging strand. DNA Polymerase III is a core enzyme in replication. It is a holozyme and consisted of various subunits. It is very fast and has high process rate. DNA polymerase III can perform two activities as 5'--->3' polymerase activity and 3'--->5' exonuclease activity, so that any mismatched base is removed. Mutations in these enzymes will lead to either decreased polymerase activity or impaired exonuclease activity, which can lead to acceptance of mismatched base pairs in replicating DNA strand. This will disturb all forthcoming life processes (transcription, translation, abnormal protein formation etc).

Ligase

Mutation in ligase will hold up joining process of newly synthesized DNA fragments (Okazaki Fragments). There will not be formation of intact DNA molecule, which in turn is equal to no DNA synthesis. This causes serious clinical issues in humans.

Single stranded binding proteins (SSB)

Single stranded binding proteins avoid premature annealing of newly synthesized DNA fragments. SSB proteins protect these ssDNA fragments from being digested by endonucleases. They prevent the formation secondary structure of ssDNA and safeguard them in their stable form.

Helicase

Helicases are responsible to separate strands of a DNA double helix, for replication. In humans, defects in helicases in humans can lead to genetic disorders showing genomic instability and predisposition to cancer.

Primase generates an RNA primer for DNA polymerase for replication.

Primase is activated by DNA helicase.

Girase relieves strain in double-strand DNA for its unwinding by helicase. It is also known as DNA topoisomerase II. This causes negative supercoiling of the DNA.

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