Hereditary tyrosinemia type 1 metabolites impair DNA excision repair pathways

► Succinylacetone (SA) and p-hydroxyphenylpyruvate (pHPPA) accumulate in HT1. ► SA and pHPPA impair base- and nucleotide excision repair. ► Base excision repair more affected than nucleotide excision repair. Hereditary tyrosinemia type 1 is an autosomal recessive metabolic disorder, which is caused by a defective fumarylacetoacetate hydrolase enzyme, and consequently metabolites such as succinylacetone and p-hydroxyphenylpyruvate accumulate. We used a modified comet assay to determine the effect of these metabolites on base- and nucleotide excision repair pathways. Our results indicate that the metabolites affected the repair mechanisms differently, since the metabolites had a bigger detrimental effect on BER than on NER.