Caenorhabditis elegans NDX-4 is a MutT-type enzyme that contributes to genomic stability.
MutT enzymes prevent DNA damage by hydrolysis of 8-oxodGTP, an oxidized substrate for DNA synthesis and antimutagenic, anticarcinogenic, and antineurodegenerative functions of MutT enzymes are well established. MutT has been found in almost all kingdoms of life, including many bacterial species, yeasts, plants and mammals. However, a Caenorhabditis elegans MutT homologue was not previously identified. Here, we demonstrate that NDX-4 exhibits both hallmarks of a MutT-type enzyme with an ability to hydrolyze 8-oxodGTP and suppress the Escherichia coli mutT mutator phenotype. Moreover, we show that NDX-4 contributes to genomic stability in vivo in C. elegans. Phenotypic analyses of an ndx-4 mutant reveal that loss of NDX-4 leads to upregulation of key stress responsive genes that likely compensate for the in vivo role of NDX-4 in protection against deleterious consequences of oxidative stress. This discovery will enable us to use this extremely robust genetic model for further research into the contribution of oxidative DNA damage to phenotypes associated with oxidative stress.
The Biotechnology Centre, University of Oslo, Oslo, Norway.
Katarzyna D
KD
Arczewska
Christian
C
Baumeier
Henok
H
Kassahun
Tanima
T
Sengupta
Magnar
M
Bjørås
Jarosław T
JT
Kuśmierek
Hilde
H
Nilsen
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics; D042822:Genomic Instability; D006360:Heat-Shock Proteins / Q000235:genetics; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D011755:Pyrophosphatases / Q000235:genetics; D015533:Transcriptional Activation
D029742:Caenorhabditis elegans Proteins; D003848:Deoxyguanine Nucleotides; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; C078206:8-oxodeoxyguanosine triphosphate; D010744:Phosphoric Monoester Hydrolases; C557890:NDX-4 protein, C elegans; D011755:Pyrophosphatases; C052211:mutT protein, E coli