Targeting of O6-MeG DNA methyltransferase (MGMT) to mitochondria protects against alkylation induced cell death.
Mitochondrial DNA (mtDNA) mutations are implicated in pathogenesis of human diseases including cancer. To prevent mutations cells have developed repair systems to counteract harmful genetic changes caused by DNA damaging agents. One such DNA repair protein is the O(6)-Methylguanine-DNA methyltransferase (MGMT) that prevents certain types of alkylation damage. Yet, the role of MGMT in preventing alkylation induced DNA damage in mtDNA is unclear. We explored the idea of increasing cell survival after alkylation damage by overexpressing MGMT in mitochondria. We show that overexpression of this repair protein in mitochondria increases cell survival after treatment with the DNA damaging agent MNNG.
Rasmussen
Anne Karin
AK
Department of Life Sciences and Chemistry, Roskilde University, 4000 Roskilde, Denmark.
Rasmussen
Lene Juel
LJ
D000478:Alkylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D009153:Mutagens / Q000633:toxicity; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D019853:O(6)-Methylguanine-DNA Methyltransferase