Complementation of aprataxin deficiency by base excision repair enzymes in mitochondrial extracts. Issue 17 (29th September 2017)

• Record Type: Journal Article
• Authors: Çağlayan, Melike; Prasad, Rajendra; Krasich, Rachel; Longley, Matthew J.; Kadoda, Kei; Tsuda, Masataka; Sasanuma, Hiroyuki; Takeda, Shunichi; Tano, Keizo; Copeland, William C.; Wilson, Samuel H.
• Is Part Of: Nucleic acids research. Volume 45:Issue 17(2017)
• Page Start: 10079
• Page End: 10088
• Publication Date: 2017-09-29
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkx654
• Languages: English
• ISSNs: 0305-1048

Abstract

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) γ and pol β as possible complementing enzymes in the case of APTX deficiency. The activities of pol β 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 γ 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 β −/− cells. FEN1 also failed to provide excision of the 5′-adenylated BER intermediate in mitochondrial extracts. These results illustrate the potential role of pol β in complementing APTX deficiency in mitochondria.