![Poly I structure](https://upload.wikimedia.org/wikipedia/commons/e/ef/Poly_I_structure.jpg)
Exonucleases are
enzymes that work by cleaving
nucleotides
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules with ...
one at a time from the end (exo) of a polynucleotide chain. A
hydrolyzing
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysis ...
reaction that breaks phosphodiester bonds at either the 3′ or the
5′ end occurs. Its close relative is the
endonuclease, which cleaves
phosphodiester bonds
In chemistry, a phosphodiester bond occurs when exactly two of the hydroxyl groups () in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds. The "bond" involves this linkage . Discussion of phosphodiesters is ...
in the middle (endo) of a polynucleotide chain.
Eukaryotes and
prokaryotes have three types of exonucleases involved in the normal turnover of
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
:
5′ to 3′ exonuclease (Xrn1), which is a dependent
decapping protein; 3′ to 5′ exonuclease, an independent protein; and poly(A)-specific 3′ to 5′ exonuclease.
In both
archaea and
eukaryotes, one of the main routes of RNA degradation is performed by the multi-protein
exosome complex
The exosome complex (or PM/Scl complex, often just called the exosome) is a multi-protein intracellular Protein complex, complex capable of degrading various types of RNA (ribonucleic acid) molecules. Exosome complexes are found in both eukaryo ...
, which consists largely of 3′ to 5′
exoribonucleases
An exoribonuclease is an exonuclease ribonuclease, which are enzymes that degrade RNA by removing terminal nucleotides from either the 5' end or the 3' end of the RNA molecule. Enzymes that remove nucleotides from the 5' end are called ''5'-3' ex ...
.
Significance to polymerase
RNA
polymerase II is known to be in effect during transcriptional termination; it works with a 5' exonuclease (human gene Xrn2) to degrade the newly formed transcript downstream, leaving the polyadenylation site and simultaneously shooting the polymerase. This process involves the exonuclease's catching up to the pol II and terminating the transcription.
Pol I
DNA polymerase I (or Pol I) is an enzyme that participates in the process of prokaryotic DNA replication. Discovered by Arthur Kornberg in 1956, it was the first known DNA polymerase (and the first known of any kind of polymerase). It was initia ...
then synthesizes DNA nucleotides in place of the RNA primer it had just removed. DNA polymerase I also has 3' to 5' and 5' to 3' exonuclease activity, which is used in editing and proofreading DNA for errors. The 3' to 5' can only remove one mononucleotide at a time, and the 5' to 3' activity can remove mononucleotides or up to 10 nucleotides at a time.
''E. coli'' types
![Exo nu](https://upload.wikimedia.org/wikipedia/commons/b/b3/Exo_nu.jpg)
In 1971, Lehman IR discovered exonuclease I in ''
E. coli''. Since that time, there have been numerous discoveries including: exonuclease, II,
III, IV,
V, VI,
VII VII or vii may refer to: the Roman numeral 7
Art and entertainment
* The Vii, a video game console
* vii, leading-tone triad, see diminished triad
* ''VII'' (Blitzen Trapper album)
* ''VII'' (Just-Ice album)
* ''VII'' (Teyana Taylor album)
* ...
, and VIII. Each type of exonuclease has a specific type of function or requirement.
''Exonuclease I'' breaks apart single-stranded DNA in a 3' → 5' direction, releasing deoxyribonucleoside 5'-monophosphates one after another. It does not cleave DNA strands without terminal 3'-OH groups because they are blocked by phosphoryl or acetyl groups.
''Exonuclease II'' is associated with DNA polymerase I, which contains a 5' exonuclease that clips off the RNA primer contained immediately upstream from the site of DNA synthesis in a 5' → 3' manner.
Exonuclease III
Exonuclease III (ExoIII) is an enzyme that belongs to the exonuclease family. ExoIII catalyzes the stepwise removal of mononucleotides from 3´-hydroxyl termini of double-stranded DNA. A limited number of nucleotides are removed during each bindi ...
has four catalytic activities:
* 3' to 5' exodeoxyribonuclease activity, which is specific for double-stranded DNA
* RNase activity
* 3' phosphatase activity
* AP endonuclease activity (later found to be called endonuclease II).
Exonuclease IV adds a water molecule, so it can break the bond of an oligonucleotide to nucleoside 5' monophosphate. This exonuclease requires Mg 2+ in order to function and works at higher temperatures than exonuclease I.
Exonuclease V is a 3' to 5' hydrolyzing enzyme that catalyzes linear double-stranded DNA and single-stranded DNA, which requires Ca2+. This enzyme is extremely important in the process of
homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
.
Exonuclease VIII is 5' to 3' dimeric protein that does not require ATP or any gaps or nicks in the strand, but requires a free 5' OH group to carry out its function .
Discoveries in humans
The 3' to 5' human type endonuclease is known to be essential for the proper processing of histone pre-mRNA, in which U7 snRNP directs the single cleavage process. Following the removal of the downstream cleavage product (DCP)
Xrn1 continues to further breakdown the product until it is completely degraded. This allows the nucleotides to be recycled.
Xrn1 is linked to a co-transcriptional cleavage (CoTC) activity that acts as a precursor to develop a free 5' unprotected end, so the exonuclease can remove and degrade the downstream cleavage product (DCP). This initiates transcriptional termination because one does not want DNA or RNA strands building up in their bodies.
Discoveries in yeast
CCR4-Not
Carbon Catabolite Repression—Negative On TATA-less, or CCR4-Not, is a multiprotein complex that functions in gene expression. The complex has multiple enzymatic activities as both a poly(A) 3′-5′ exonuclease and a ubiquitin ligase. The com ...
is a general transcription regulatory complex in
budding yeast
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been ...
that is found to be associated with
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
metabolism, transcription initiation, and mRNA degradation. CCR4 has been found to contain
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
and single-stranded
DNA 3' to 5' exonuclease activities. Another component associated with the
CCR4-Not
Carbon Catabolite Repression—Negative On TATA-less, or CCR4-Not, is a multiprotein complex that functions in gene expression. The complex has multiple enzymatic activities as both a poly(A) 3′-5′ exonuclease and a ubiquitin ligase. The com ...
is CAF1 protein, which has been found to contain 3' to 5' or 5' to 3' exonuclease domains in the
mouse and ''
Caenorhabditis elegans''. This protein has not been found in yeast, which suggests that it is likely to have an abnormal exonuclease domain like the one seen in a metazoan. Yeast contains
Rat1 and Xrn1 exonuclease. The Rat1 works just like the human type (Xrn2) and
Xrn1 function in the cytoplasm is in the 5' to 3' direction to degrade RNAs (pre-5.8s and 25s rRNAs) in the absence of Rat1.
Discoveries in Coronaviruses
In beta
Coronaviruses, including
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
, a proof reading exonuclease, nsp14-ExoN, that is part of the viral genome, is responsible for recombination that is implicated in novel strain emergence.
References
External links
*
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EC 3.1
Genetics techniques