Kassahun 2018 DNA Repair (Amst)
| Kassahun H, SenGupta T, Schiavi A, Maglioni S, Skjeldam HK, Arczewska K, Brockway NL, Estes S, Eide L, Ventura N, Nilsen H (2018) Constitutive MAP-kinase activation suppresses germline apoptosis in NTH-1 DNA glycosylase deficient C. elegans. DNA Repair (Amst) 61:46-55. |
Kassahun H, SenGupta T, Schiavi A, Maglioni S, Skjeldam HK, Arczewska K, Brockway NL, Estes S, Eide L, Ventura N, Nilsen H (2018) DNA Repair (Amst)
Abstract: Oxidation of DNA bases, an inevitable consequence of oxidative stress, requires the base excision repair (BER) pathway for repair. Caenorhabditis elegans is a well-established model to study phenotypic consequences and cellular responses to oxidative stress. To better understand how BER affects phenotypes associated with oxidative stress, we characterised the C. elegans nth-1 mutant, which lack the only DNA glycosylase dedicated to repair of oxidative DNA base damage, the NTH-1 DNA glycosylase. We show that nth-1 mutants have mitochondrial dysfunction characterised by lower mitochondrial DNA copy number, reduced mitochondrial membrane potential, and increased steady-state levels of reactive oxygen species. Consistently, nth-1 mutants express markers of chronic oxidative stress with high basal phosphorylation of MAP-kinases (MAPK) but further activation of MAPK in response to the superoxide generator paraquat is attenuated. Surprisingly, nth-1 mutants also failed to induce apoptosis in response to paraquat. The ability to induce apoptosis in response to paraquat was regained when basal MAPK activation was restored to wild type levels. In conclusion, the failure of nth-1 mutants to induce apoptosis in response to paraquat is not a direct effect of the DNA repair deficiency but an indirect consequence of the compensatory cellular stress response that includes MAPK activation. • Keywords: Apoptosis, Base excision repair, C. elegans, NTH-1, Oxidative stress • Bioblast editor: Kandolf G • O2k-Network Lab: NO Oslo Eide L
Labels: MiParea: Respiration, mtDNA;mt-genetics
Organism: Caenorhabditis elegans
Preparation: Intact organism
HRR: Oxygraph-2k
Labels, 2018-02
