Complementation of aprataxin deficiency by base excision repair enzymes in mitochondrial extracts.

ABSTRACT: Mitochondrial aprataxin (APTX) protects the mitochondrial genome from the consequence of ligase failure by removing the abortive ligation product, i.e. the 5'-adenylate (5'-AMP) group, during DNA replication and repair. In the absence of APTX activity, blocked base excision repair (BER) intermediates containing the 5'-AMP or 5'-adenylated-deoxyribose phosphate (5'-AMP-dRP) lesions may accumulate. In the current study, we examined DNA polymerase (pol) ? and pol ? as possible complementing enzymes in the case of APTX deficiency. The activities of pol ? lyase and FEN1 nucleotide excision were able to remove the 5'-AMP-dRP group in mitochondrial extracts from APTX-/- cells. However, the lyase activity of purified pol ? was weak against the 5'-AMP-dRP block in a model BER substrate, and this activity was not able to complement APTX deficiency in mitochondrial extracts from APTX-/-Pol ?-/- cells. FEN1 also failed to provide excision of the 5'-adenylated BER intermediate in mitochondrial extracts. These results illustrate the potential role of pol ? in complementing APTX deficiency in mitochondria.

SUBMITTER: Caglayan M 

PROVIDER: S-EPMC5622373 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature