Exonuclease

Source: Wikipedia, the free encyclopedia.
Not to be confused with Excinuclease.
3′ to 5′ Exonuclease associated with Pol I

Exonucleases are

mRNA: 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.[1][2]

In both

exoribonucleases
.

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.[3]

Pol I 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

WRN Exonuclease with active sites in yellow

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, and VIII. Each type of exonuclease has a specific type of function or requirement.[4]

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. [5]

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 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).[6]

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.[7]

Exonuclease V is a 3' to 5' hydrolyzing enzyme that catalyzes linear double-stranded DNA and single-stranded DNA, which requires Ca2+.[8] This enzyme is extremely important in the process of homologous recombination
.

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 [citation needed].

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.[9] 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.[10]

Discoveries in yeast

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.[14][15]

Discoveries in Coronaviruses

In beta

SARS-CoV-2, a proof reading exonuclease, nsp14-ExoN, that is part of the viral genome, is responsible for recombination that is implicated in novel strain emergence.[16]

References

  1. PMID 14770007
    .
  2. S2CID 40843312
    .
  3. PMID 18413717
    .
  4. ISBN 978-0-12-122723-4
    .
  5. PMID 14235546
    .
  6. PMID 6246343. {{cite book}}: |journal= ignored (help
    )
  7. ISBN 978-0-8493-7658-0
    .
  8. PMID 10957971
    .
  9. PMID 18955505
    .
  10. PMID 15565158
    .
  11. PMID 11889047
    .
  12. PMID 7791755
    .
  13. PMID 9396823. Archived from the original
    on 2012-07-18.
  14. PMID 7515008
    .
  15. PMID 11142370
    .
  16. PMID 33465137
    .

External links
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