Spinocerebellar ataxia with axonal neuropathy

Cheryl Walton, Heidrun Interthal, Ryuki Hirano, Mustafa A M Salih, Hiroshi Takashima, Cornelius F Boerkoel

Research output: Contribution to journalArticle

Abstract

Spinocerebellar ataxia with axonal neuropathy (SCAN 1) is an autosomal recessive disorder caused by a specific point mutation (c.1478A>G, p.H493R) in the tyrosyl-DNA phosphodiesterase (TDP1) gene. Functional and genetic studies suggest that this mutation, which disrupts the active site of the Tdp1 enzyme, causes disease by a combination of decreased catalytic activity and stabilization of the normally transient covalent Tdp1-DNA intermediate. This covalent reaction intermediate can form during the repair of stalled topoisomerase I-DNA adducts or oxidatively damaged bases at the 3' end of the DNA at a strand break. However, our current understanding of the biology of Tdp1 function in humans is limited and does not allow us to fully elucidate the disease mechanism.
Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalAdvances in Experimental Medicine and Biology
Volume685
DOIs
Publication statusPublished - 2010

Keywords

  • strand break
  • replication fork
  • spinocerebellar ataxia
  • premature ovarian failure
  • axonal neuropathy

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