Actions of aprataxin in multiple DNA repair pathways

Rass, Ulrich, Ahel, Ivan and West, Stephen C (2007) Actions of aprataxin in multiple DNA repair pathways. The Journal of Biological Chemistry, 282 (13). pp. 9469-9474. ISSN 0021-9258

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Mutations in the Aptx gene lead to a neurological disorder known as ataxia oculomotor apraxia-1. The product of Aptx is Aprataxin (Aptx), a DNA-binding protein that resolves abortive DNA ligation intermediates. Aprataxin catalyzes the nucleophilic release of adenylate groups covalently linked to 5' phosphate termini, resulting in termini that can again serve as substrates for DNA ligases. Here we show that Aprataxin acts preferentially on adenylated nicks and double-strand breaks rather than on single-stranded DNA. Moreover, we show that whereas the catalytic activity of Aptx resides within the HIT domain, the C-terminal zinc finger domain provides stabilizing contacts that lock the enzyme onto its high affinity AMP-DNA target site. Both domains are therefore required for efficient AMP-DNA hydrolase activity. Additionally, we find a role for Aprataxin in base excision repair, specifically in the removal of adenylates that arise from abortive ligation reactions that take place at incised abasic sites in DNA. We suggest that Aprataxin may have a general proofreading function in DNA repair, removing DNA adenylates as they arise during single-strand break repair, double-strand break repair, and in base excision repair.

Item Type: Article
Keywords: DNA repair, DNA single-strand break repair,DNA double-strand break repair, base excision repair, abortive DNA ligation, histidine triad, AMP-DNA, DNA de-adenylation, aprataxin, neurodegenerative disease, ataxia with oculomotor apraxia 1
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science > Q Science (General) > Q0179.9 Research
Q Science > Q Science (General)
Depositing User: Ulrich Rass
Date Deposited: 26 Sep 2018 08:29
Last Modified: 26 Sep 2018 08:29

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