2007年
Aprataxin, causative gene product for EAOH/AOA1, repairs DNA single-strand breaks with damaged 3'-phosphate and 3'-phosphoglycolate ends.
Nucleic acids research
- 巻
- 35
- 号
- 11
- 開始ページ
- 3797
- 終了ページ
- 809
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1093/nar/gkm158
- 出版者・発行元
- OXFORD UNIV PRESS
Aprataxin is the causative gene product for early-onset ataxia with ocular motor apraxia and hypoalbuminemia/ataxia with oculomotor apraxia type 1 (EAOH/AOA1), the clinical symptoms of which are predominantly neurological. Although aprataxin has been suggested to be related to DNA single-strand break repair (SSBR), the physiological function of aprataxin remains to be elucidated. DNA single-strand breaks (SSBs) continually produced by endogenous reactive oxygen species or exogenous genotoxic agents, typically possess damaged 3'-ends including 3'-phosphate, 3'-phosphoglycolate, or 3'-alpha, beta-unsaturated aldehyde ends. These damaged 3'-ends should be restored to 3'-hydroxyl ends for subsequent repair processes. Here we demonstrate by in vitro assay that recombinant human aprataxin specifically removes 3'-phosphoglycolate and 3'-phosphate ends at DNA 3'-ends, but not 3'-alpha, beta-unsaturated aldehyde ends, and can act with DNA polymerase beta and DNA ligase III to repair SSBs with these damaged 3'-ends. Furthermore, disease-associated mutant forms of aprataxin lack this removal activity. The findings indicate that aprataxin has an important role in SSBR, that is, it removes blocking molecules from 3'-ends, and that the accumulation of unrepaired SSBs with damaged 3'-ends underlies the pathogenesis of EAOH/AOA1. The findings will provide new insight into the mechanism underlying degeneration and DNA repair in neurons.
- リンク情報
-
- DOI
- https://doi.org/10.1093/nar/gkm158
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902264294779816
- CiNii Articles
- http://ci.nii.ac.jp/naid/80018371325
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/17519253
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920238
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000247817500027&DestApp=WOS_CPL
- ID情報
-
- DOI : 10.1093/nar/gkm158
- ISSN : 0305-1048
- eISSN : 1362-4962
- J-Global ID : 200902264294779816
- CiNii Articles ID : 80018371325
- PubMed ID : 17519253
- PubMed Central 記事ID : PMC1920238
- Web of Science ID : WOS:000247817500027