Errors In DNA Replication: 13 Facts Most Beginners Don’t Know

DNA replication can sometimes be at fault because of the addition or deletion of the new nucleotide bases. Let us see how errors occur when DNA replicates.

Errors in DNA replication are known as Strand Slippage where the new nucleotide bases are added or deleted by mutation or permanent sequence changes etc. of DNA. Freshly secreted loops of strands go out a bit. For this change, the result is an addition or deletion of an extra nucleotide base.

There are mainly three types of errors in DNA replication. They are Base substitutions, Deletions, and Insertions. If the error is not corrected, it may cause cancer. Here, the repair mechanism of DNA corrects all the errors.

Let us discuss if DNA replication is accurate, what all errors are there in DNA replication, causes and effects of errors in DNA replication and many other related topics in this article.

Is DNA replication accurate?

The rate of error in DNA replication is very less. Let us see if DNA replication is accurate or not.

DNA replication is accurate that the rate of errors in DNA replication can be negligible. This is formed in a way as the genome stability is dependent on the accuracy of DNA replication. But the faulty genomes can be fatal for the animal body due to the mutation of the whole gene pool.

The accuracy in DNA replication is well defined because of three factors. They are Nucleotide selectivity, Proofreading, and Mismatch repair. These factors are the main cause of fewer errors in DNA replication.

What are errors in DNA replication?

Errors in DNA replication is mainly due to the depurination of the whole genome pool. Let us discuss what all are the possible errors in DNA replication.

Errors in DNA replication are divided into three types: Replication errors, depurination of DNA, and damage of DNA by the generation of active oxygen species.

Let us see more information regarding errors in DNA replication below:

  • The breakage is caused by the water molecule which results in a nucleotide that is purine free. This can not be used in replication.
  • The purine free can not function during the replication of DNA as the template.
  • Loss of amino group from the nucleotide is also caused by the deamination for not functioning as the template during the errors in DNA replication by the water reaction.
  • These non intended causes are corrected by the repair process of DNA again.
  • But a new nucleotide is then added becoming the permanent mutation.
  • It occurs during the synthesis of a new strand.
  • Accumulated mutations or permanent sequence changes are the cause of these bad behaviors in cells’ DNA.

Causes of errors in DNA replication

There are several reasons for the cause of errors in DNA replication. Let us see what they are in detail.

Errors in DNA replication are mainly caused due to the dissimilar nature of base pairs. They can either be different in nature or can be non tautomeric in chemical forms.

The main three causes of errors in DNA replication are discussed in detail below:

1. Deletion : Deletion is one of the basic errors in DNA replication. It causes the shift of frame of the entire gene pool. It changes the sequence of DNA by destroying one (at least) or more nucleotides.

2. Insertion : Insertion is another basic error in DNA replication. It causes the shift of frame of the entire gene pool. It changes the sequence of DNA by adding one (at least) or more nucleotide base pairs.

3. Base substitutions : Base substitution is also one of the important errors in DNA replication. It replaces the proper nucleotide with any other nucleotide which changes the whole gene pool. It can also change one amino acid with another.

DNA replication error rate

As discussed earlier, there is a slight chance that errors might occur in DNA replication. Let us look at the rate at which errors in DNA occur.

DNA replication error rate is one in 10^10 nucleotides during the synthesis of DNA. It is so less but the effects can be fatal. It is 10^-9 to 10^-11 errors in DNA replication as per base pair. The high fidelity of the process is very crucial for maintaining the accuracy of genetic identity.

For example, E. coli makes only one error for per billion copies of nucleotides. It finishes its replication within 60 minutes and can replicate 2000 nucleotides per second. Compared to the human body, its number of mistakes are low.

Effects of errors in DNA replication

The effects of errors in DNA replication are mainly fatal. Let us look at the effects of errors in DNA replication in detail.

Errors in DNA replication can result in tumors, cancer, etc. Errors can lead to mutations which further result in tumors and finally cause cancer.

Some of the effects of errors in DNA replication are-

1. Germline mutation

2. Chromosomal alterations

3. Frameshift mutation

4. Point mutation

If errors in DNA are not corrected on time by proof reading, mutations occur. Some effect of errors in DNA replication are- sickle cell anemia, one form of beta thalassemia, cystic fibrosis, etc.

Can errors in DNA replication results in mutations?

The repair mechanism corrects all the faults that occur during the DNA replication. Let us discuss if errors in DNA replication results in mutations.

Errors in DNA replication can result in the mutations like the permanent mutation. In the DNA repair mechanism, the repair enzymes find the mistakes that occur and removes them. Subsequently, they recruit the right nucleotide in place. But some replication errors pass these processes and mutations occur.

For example, some base substitution mutations are point mutations like a silent, missense, and nonsense mutations. Besides some mutations like frame shift mutation, germline or somatic mutation. The main types of mutations are Deletion, Inversion, Insertion, Duplication, Translocation, Gene Amplification, etc.

How errors in DNA replication can lead to mutations?

Errors in DNA replication can lead to mutation even in permanent mutation. So, it plays a very important role. The formation of some figures helps to lead. Let us explain this.

Listed below shows how errors in DNA replication can lead to mutations in detail:

  • Errors in DNA replication can lead to mutations especially in the case of TNR (trinucleotide repeat) expansion.
  • This repeat has the contribution to the slippage of DNA polymerase during replication.
  • The secondary structures are formed like Intra strand hairpins.
  • Such secondary structures are formed due to the repeat sequence of trinucleotide expansions.
  • For this, the enzymes get back and replicate the former portion.
  • As result, the repair does not take place.As the repair does not occur for the mistakes of the errors in DNA replication, it follows the previous path.
  • For this, the faults of DNA replication go on and as a result, mutation specifically permanent mutation occurs.

Which type of mutations are caused by random errors in DNA replication?

There are three types of mutations occur during the time of errors in DNA replication. But there are more types under deletion, insertion, base substitution. Let us discuss them.

Types of mutations like point mutation, chromosomal mutation, germline or somatic mutation, and frameshift mutation are caused by random errors in DNA replication. Under point mutation, there are more types. Besides, these mutations can be caused by various reason.

The mutation is caused by the substance named mutagen. It can be radiation, chemicals, toxic materials, or something else. They are very much spontaneous in the environment.

Point Mutation

Point mutation is a type of mutation where only one nucleotide is changed or shifted or replaced. There are three types of point mutations in errors of DNA replication. They are silent, missense, and nonsense mutation.

Chromosomal Mutation

In case of chromosomal mutation, the structure of chromosome is changed during the errors of DNA replication. They can be altered or changes by the core.

Frameshift Mutation

In a Frameshift mutation, nucleotides can be added or deleted in the errors in DNA replication. For this, the shifting of the whole DNA pool frame is changed. One or many nucleotides can do this shift.

Induced mutations are initiated by errors in DNA replication

A mutation alters the whole DNA sequence of a particular organism. Let us explore more about induced mutations which are initiated by errors in DNA replication.

Induced mutations are initiated by the errors in DNA replication as during the division of cells, mutagens are exploded in the DNA, which during the replication process, lead them to the mutation.

Induced mutation then lead to permanent mutation. A gene mutation can be caused in many genes or can be the cause of a loss of one or more genes. It can change DNA nucleotides (one or more).

How are DNA replication errors corrected?

Errors in DNA replication are corrected by some of the reliable process. Let us see what they are in detail.

DNA replication errors are corrected by mainly two procedures which are proofreading and mismatch repair. Proofreading is where the errors in DNA replication are reformed during the time of DNA replication and mismatch repair is where the errors are reformed after the DNA replication.

Proofreading

Proofreading creates a structure that invites the other proteins to repair the mistake because the proteins in it are able to restrain the errors in DNA replication.

When proofreading occurs, the polymerase form of DNA identifies errors in DNA replication. Then, it replaces the wrong inserted or deleted nucleotide. Being corrected, replication continues with its own flow.

Mismatch repair

Mismatch repair is when the mistakes are corrected after the fork formation is not repaired during the DNA replication. But it is specific for individual strands. Errors in DNA replication are reformed after the process as it is the final correction.

In mismatch repair, there are certain genes which helps to prevent the errors in DNA replication after the replication finishes. The genes are PMS2, MLH1, MSH2, MSH6.

errors in dna replication
Correction of Replication Error from wikipedia

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Why DNA replication errors are more impactful than errors in transcription?

Replication is a very prominent process than transcription. Besides, the errors of RNA transcription are not impactful like the errors in DNA replication. Let us discuss this.

DNA replication errors are more impactful than the errors in the transcription of RNA as it is not heritable like the errors in DNA replication. Besides, a very low number of proteins are changed during the transcription. The change is not very injurious like the replication and can be cured.

For example, the rate of errors in transcription is 2.3*10^-5 in mRNA to 5.2*10^-5 in rRNA per nucleotide for a certain species of bacteria. But it is not transmitted to the next generation like the errors in DNA replication.

Can cell repair DNA replication error?

Cell can repair some of the DNA replication errors. It is a very fortunate thing that cells have some of the superior quality to rectify the mistakes. Let us explore more.

A cell can repair DNA replication errors in some cases. Cells have specific properties to combat some mistakes of errors in DNA replication. Cells can also fix them at a certain percentage. During the cell cycle, by proof reading and mismatch repair, cells can manage them.

Some of the repair mechanisms for combating and fixing the errors in DNA replication during the cell cycle are direct reversal of the damage, excision repair, post replication repair, BER (base excision repair), NER (nucleotide excision repair), MMR (mismatch repair), HR (homologous recombination), and NHEJ (non homologous end joining).

Why are errors in DNA replication so rare?

Errors in DNA replication is so rare that one error occurs in billions of nucleotides while copying. Let us understand the reason behind this.

Errors in DNA replication are so rare because of proofreading and mismatch repair mechanisms of repairing the mistakes. It occurs occasionally when the wrong nucleotides are inserted by the polymerase of DNA. If it is not, they can lead to mutation which can lead to cancer.

Proofreading solves all the pre-replication mistakes and mismatch solves the post replication faults. As a result, the mistake rate is one in every 10^4 to 10^5 nucleotide in synthesis. Even if there are some faults, the rate is less than 0.001%.

Conclusion

At the end of the article, it is proved that errors in DNA replication are very rare and if the error stays after the repair mechanisms, it can lead it to a permanent mutation (though many small mutations) which then results in cancer or other fatal health conditions for the next generations too. As DNA replication is a very crucial and important procedure during the cell cycle, it is a highly protected system.

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