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Difference Between Exonuclease and Endonuclease

Difference between Exonuclease and Endonuclease

Before understanding the difference between exonuclease and endonuclease, know about what is a nuclease. It is a group of enzymes that function to hydrolyze the nucleic acids (DNA or RNA). Basically, they can dissociate a phosphodiester backbone that interlinks different nucleotides. They are generally categorized into two types, depending upon the mechanism of action and location in the nucleic acid. These are Exonucleases and endonucleases.

The main difference between exonuclease and endonuclease is the point where it divides. As the name indicates, exonuclease splits the bond from the outer ends, whereas endonuclease cleaves the bond that is inside the polynucleotide chain. Before moving further, let’s take a glance at its comparison chart below.

Comparison Table

Basis of ComparisonExonucleaseEndonuclease
Main FunctionThese enzymes work by cleaving a polynucleotide chain from the outer endsThese enzymes work by cleaving a polynucleotide chain from inside
SpecificityThey are usually non-specificThey can be either specific or non-specific. The specific endonucleases are termed as Restriction Endonucleases.
Lag PeriodThere is no lag period before the process startsEndonucleases have a lag period prior to their activity
Final ResultsFinal results are individual nucleosides or nucleotidesFinal results are oligonucleotides
Nature of EndsSticky endsBlunt or sticky ends
Effect on PathogensNo effect on the entry of pathogensBlocks the entryway for pathogens
ExamplesDNA polymerase-III, snake venom, lizard venom, etc.DNases, EcoRI, Hind-III, etc.

Explain Exonuclease

The enzymes that split a DNA sequence from either 5’ or 3’ end of a polynucleotide chain are called exonucleases. These nucleases are essential to both, eukaryotes and archaea, degrading their RNA through the multi-protein exosome, including different exoribonucleases. Moreover, they are also present in venoms of lizards and snakes, cleaving the DNA sequence of their essential proteins. Exonucleases are crucial in the replication process as they function with the RNA polymerase-II to further replace the transcript with DNA nucleotide.

Explain Endonuclease

The enzymes that split phosphodiester bonds from inside a polynucleotide chain are called endonucleases. Such nucleases can either be specific or non-specific to the DNA sequencing. The specific ones are known as Restriction Endonucleases, obtained from numerous archaea and bacteria. The bond that cleaves from a single-stranded end called the sticky end are further hybridized by DNA ligase. It results in the formation of DNA called Recombinant DNA, and the procedure is known as Recombination.

Know the Similarities Between Exonuclease & Endonuclease

Both exonucleases and endonucleases are types of nuclease (an enzyme), so they have a few similarities too. Let’s have a look at them below!

Acts on Polynucleotide Chain: Both of these nucleases act on the polynucleotide chain to hydrolyze it.

Nucleic Acid: The exonuclease and endonuclease deal with the nucleic acid.

Effects DNA & RNA: They can influence either DNA or RNA.

Figure Out the Dissimilarities Between Exonuclease & Endonuclease

There are numerous dissimilarities between exonuclease and endonuclease if you read them in detail. So, let’s move on!

1. Point of Cleavage


As the name suggests, these enzymes cleave a bond from the ends.


Such enzymes break a nucleotide arrangement from the inside (middle).

2.End Products


The cleavage of DNA sequence by exonuclease results in individual Nucleosides or Nucleotides.


The cleavage of DNA sequence by endonuclease results in Oligonucleotides.



As these enzymes divide a bond from the ends, so usually non-peculiar or non-specific.


Endonucleases can be specific or non-specific. The specific ones are referred to as restriction endonucleases that cleave some particular sites of a DNA sequence.

4.Influence of Circular DNA


Due to being non-specific in nature, exonucleases have greater activity towards linear DNA and lesser towards circular DNA.


The restriction endonucleases specifically cleave a bond within circular DNA.

5. Nature of Ends


They form sticky ends that should always remain free for cleavage.


They might result in blunt or sticky ends. Moreover, there is no necessity for the free 3’ or 5’ ends of a polynucleotide chain.

6.Protective Characteristics


They do not have any protective property because of the non-specific nature.


They specifically protect a body against the entrance of pathogenic microorganisms.

7. Common Examples


A few common examples include Exonuclease-I, snake/lizard venom, and Xrn1, etc.


Some common examples of endonuclease are Deoxyribonuclease-I, BamHI, and EcoRI, etc.


Both of the nucleases have a significant role in genetics, as we have discussed above. The main difference between exonuclease and endonuclease lies in its location and functioning. Exonucleases discharge the heterochromatin portion to maintain the uprightness of DNA. On the other hand, the cleavage by endonuclease from the middle protects nucleic acid from harmful particles. Furthermore, they are broadly used in genetic engineering, recombinant DNA technology, diagnostics and gene editing, etc.

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