nucleotide incision repair (NIR)

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DESCRIPTION:

The DNA glycosylase pathway, which requires the sequential action of two enzymes for the incision of DNA, presents a serious problem for the efficient repair of oxidative DNA damage, because it generates genotoxic intermediates such as abasic sites and/or blocking 3'-end groups that must be eliminated by additional steps before DNA repair synthesis can be initiated. Besides the logistical problems, biological evidence hints at the existence of an alternative repair pathway.

Nfo-like endonucleases nick DNA on the 5' side of various oxidatively damaged bases, generating 3'-hydroxyl and 5'-phosphate termini. Nfo-like endonucleases function next to each of the modified bases, including 5,6-dihydrothymine, 5,6-dihydrouracil, 5-hydroxyuracil and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine residues. The 3'-hydroxyl terminus (3'OH) provides the proper end for DNA repair synthesis; the dangling damaged nucleotide on the 5' side is then a good substrate for human flap-structure endonuclease and for DNA polymerase I of E. coli.

ABBREVIATIONS:
NIR


OTHER NAME(S):
alternative nucleotide incision repair pathway


DAMAGES RECOGNIZED AND REMOVED:


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ORTHOLOGY CLASS Homo sapiens L. (human) [HSA] Mus musculus L. (mouse) [MMU] Caenorhabditis elegans Maupas (nematode) [CEL] Drosophila melanogaster Meigen (fruit fly) [DME] Saccharomyces cerevisiae Meyen ex E.C. Hansen (budding yeast) [SCE] Schizo-saccharomyces pombe Lindner (fission yeast) [SPO] Escherichia coli Migula (bacterium) K-12 MG1655 [ECO] Arabidopsis thaliana (L.) Heynh. (mouse-ear cress) [ATH]
ko:K01151 (deoxyribonuclease IV [EC:3.1.21.2]) Nfo (endo IV)
ko:K05982 (deoxyribonuclease V [EC:3.1.21.7]) ENDOV Endov Nfi (endo V) AT4G31150

References:

  • New insights in the removal of the hydantoins, oxidation product of pyrimidines, via the base excision and nucleotide incision repair pathways.
    Redrejo-Rodríguez M, Saint-Pierre C, Couve S, Mazouzi A, Ishchenko AA, Gasparutto D, Saparbaev M.
    PLoS One, 2011 , : [PUBMED]
  • Uncoupling of the base excision and nucleotide incision repair pathways reveals their respective biological roles.
    Ishchenko AA, Deprez E, Maksimenko A, Brochon JC, Tauc P, Saparbaev MK.
    Proc Natl Acad Sci U S A., 2006 , : [PUBMED]
  • Alternative nucleotide incision repair pathway for oxidative DNA damage.
    Ischenko AA, Saparbaev MK.
    Nature, 2002 , : [PUBMED]

Last modification date: Dec. 27, 2011