Spinocerebellar ataxia with axonal neuropathy.

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.

• Authors: Cheryl Walton, Heidrun Interthal, Ryuki Hirano, Mustafa A M Salih, Hiroshi Takashima, Cornelius F Boerkoel
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 685 Pg. 75-83 ( 2010) ISSN: 0065-2598 [Print] United States
• PMID: 20687496 (Publication Type: Journal Article, Review)

Chemical References

• DNA
• Phosphoric Diester Hydrolases
• TDP1 protein, human
• DNA Topoisomerases, Type I

Topics

• Chromosome Disorders (enzymology, genetics, pathology)
• DNA (genetics, metabolism)
• DNA Breaks
• DNA Repair (genetics)
• DNA Repair-Deficiency Disorders (enzymology, genetics, pathology)
• DNA Topoisomerases, Type I (genetics, metabolism)
• Humans
• Phosphoric Diester Hydrolases (genetics, metabolism)
• Point Mutation
• Spinocerebellar Ataxias (enzymology, genetics, pathology)