The 3′–5′ exonucleases

  title={The 3′–5′ exonucleases},
  author={Igor V. Shevelev and Ulrich Hübscher},
  journal={Nature Reviews Molecular Cell Biology},
Over the past few years, several new 3′–5′ exonucleases have been identified. In vitro studies of these enzymes have uncovered much about their potential functions in vivo, and certain organisms with a defect in 3′–5′ exonucleases have an increased susceptibility to cancer, especially under conditions of stress. Here, we look at not only the newly discovered enzymes, but also at the roles of other 3′–5′ exonucleases in the quality control of DNA synthesis, where they act as proofreading… 

The Multiple Biological Roles of the 3′→5′ Exonuclease of Saccharomyces cerevisiae DNA Polymerase δ Require Switching between the Polymerase and Exonuclease Domains

It is concluded that the three biological functions of the 3′→5′ exonuclease addressed in this study are performed intramolecularly within the replicating holoenzyme.

A Novel Single-Strand Specific 3′–5′ Exonuclease Found in the Hyperthermophilic Archaeon, Pyrococcus furiosus

A novel nuclease may be involved in a DNA repair pathway conserved in the living organisms as a specific member for some hyperthermophilic archaea, and lacks similarity to any other proteins with known function, including hitherto reported 3′–5′ exonucleases.

A 3′-5′ exonuclease activity embedded in the helicase core domain of Candida albicans Pif1 helicase

It is uncovered that Candida albicans Pif1 (CaPif1) displays a 3′-5′ exonuclease activity besides its main helicase activity, which may suggest a biochemical basis for mechanistic studies of Pif 1 family helicases.

Modulation of the 3′→5′-Exonuclease Activity of Human Apurinic Endonuclease (Ape1) by Its 5′-incised Abasic DNA Product*

Roles for the Ape1 exonuclease during BER are suggested after both DNA repair synthesis and excision of the abasic deoxyribose-5-phosphate by polymerase β.

The Presence of 3′–5′ Exonuclease Activity in Rat Brain Neurons and Its Role in Template-Driven Extension of 3′-Mismatched Primers by DNA-Polymerase β in Aging Neurons

The results revealed that in the case of duplexes with a mismatch at 3′-end of primer, significant extension by DNA polymerase β has taken place only after the removal of the mismatched base, thus indicating the presence of a proof reading 3′–5′ exonuclease activity in neuronal extracts of all ages.

The Human TREX2 3′ → 5′-Exonuclease Structure Suggests a Mechanism for Efficient Nonprocessive DNA Catalysis*

The human TREX2 catalytic residues overlay with the bacterial DnaQ family of 3′-exonucleases confirming the structural conservation of the catalytic sites despite limited sequence identity, and mutations of these residues decrease the still measurable activity by ∼105-fold, confirming their catalytic role.

Ratio of 3′ → 5′-exonuclease and DNA polymerase activities in normal and cancer cells of rodents and human

In experiments on cells growing in culture, it has been found that in adult human dermal fibroblasts the value of ratio of activity of 3′ → 5′-exonucleases to the DNA polymerase activity (3′- exo/pol) exceeds this ratio for HeLa cells.

A sequence-dependent exonuclease activity from Tetrahymena thermophila

The specificities of the enzyme indicate that this novel Tetrahymena exonuclease is distinct from Exo1 and has properties required for 3'-overhang formations at telomeres.

3′-End Polishing of the Kinetoplastid Spliced Leader RNA Is Performed by SNIP, a 3′→5′ Exonuclease with a Motley Assortment of Small RNA Substrates

The identification and characterization of a nonexosomal, 3′→5′ exonuclease required for SL RNA 3′-end formation in Trypanosoma brucei is reported and it is speculated that SNIP is part of an organized nucleoplasmic machinery responsible for processing of SL RNA.

[Antimutagenic role of autonomous 3'-->5'-exonucleases].

An investigation of thirty objects from all three kingdoms of life has shown that AE increase significantly the intracellular ratio of 3′ → 5′-exonuclease to DNA polymerase activities in a wide phylogenetic variety of species, which always leads to the increasing fidelity of DNA biosynthesis.



The Role of 3′-5′ Exonucleolytic Proofreading and Mismatch Repair in Yeast Mitochondrial DNA Error Avoidance*

The sequencing of mtDNA point mutations in the wild-type strain and in proofreading and mismatch-repair deficient mutants shows that mismatch repair contributes to elimination of the transitions while exonucleolytic proofreading preferentially repairs transversions, and more specifically A to T (or T to A) transversions.

The TREX2 3′→ 5′ Exonuclease Physically Interacts with DNA Polymerase δ and Increases Its Accuracy

The data suggested that autonomous 3′→ 5′ exonucleases, such as TREX2, through its association with pol I can guarantee high fidelity under difficult conditions in the cell and can add to the accuracy of the DNA replication machinery, thus preventing mutagenesis.

Human Exonuclease I Is Required for 5′ and 3′ Mismatch Repair*

The involvement of hEXOI in 3′-heteroduplex repair suggests that it has a regulatory/structural role in assembly of the3′-excision complex or that the protein possesses a cryptic 3′ to 5′ hydrolytic activity.

The 3′ → 5′ exonucleases of both DNA polymerases δ and ε participate in correcting errors of DNA replication in Saccharomyces cerevisiae

DNA polymerases II (ε) and III(δ) are the only nuclear DNA polymerases known to possess an intrinsic 3′ → 5′ exonuclease in Saccharomyces cerevisiae. We have investigated the spontaneous mutator

The 3′→5′ Exonucleases of DNA Polymerases δ and ɛ and the 5′→3′ Exonuclease Exo1 Have Major Roles in Postreplication Mutation Avoidance in Saccharomyces cerevisiae

Surprisingly, the mutation rate in an exo1 pol3-01 mutant was comparable to that in an msh2 pol3 -01 mutant, suggesting that they participate directly in postreplication mismatch repair as well as in other DNA metabolic processes.

An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3′ mispaired DNA

The exonuclease activity of APE1 can remove the anti-HIV nucleoside analogues 3′-azido-3′-deoxythymidine and 2′,3″-didehydro-2′, 3′ -dideoxymidine from DNA, suggesting thatAPE1 might have an impact on the therapeutic index of antiviral compounds in this category.

The 3′‐5′ exonuclease of DNA polymerase I of Escherichia coli: contribution of each amino acid at the active site to the reaction.

The pH‐dependence of the 3′‐5′ exonuclease reaction is consistent with a mechanism in which nucleophilic attack on the terminal phosphodiester bond is initiated by a hydroxide ion coordinated to one of the enzyme‐bound metal ions.

Exonuclease IX of Escherichia coli.

A new exonuclease found in E.coli is identified that acts preferentially on single-stranded DNA as a 3'-->5' exonUClease and also functions as a3'-phosphodiesterase on DNA containing 3'-incised apurinic/apyrimidinic sites to remove the product trans -4-hydroxy-2-pentenal 5-phosphate.