Endogenous metabolism releases genotoxic formaldehyde

LUCAS B. PONTEL; BURGOS-BARRAGAN G; RUI YU; SWENBERG JA; KJ PATEL

Simposio; Frontiers in Stem Cells and Cancer, EMBO-EMBL symposium,; 2015

EMBO-EMBL

Formaldehyde is the simplest and one of the most reactive aldehydes. It can be generated by endongenous metabolism close to DNA. For example, from histone and DNA demethylation reactions. To counteract this genotoxic molecule cells evolved the enzyme ADH5 (Alcohol dehydrogenase 5). This enzyme oxidizes formaldehyde, while the genome is protected by the Fanconi DNA repair pathway. This dual protection operates in haematopoietic stem cells to ensure blood production. Its inactivation can drive bone marrow failure and leukaemi