Abstract Spinocerebellar ataxia with axonal neuropathy (SCAN1) 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. © 2010 Landes Bioscience and Springer Science+Business Media.
CITATION STYLE
Walton, C., Interthal, H., Hirano, R., Salih, M. A. M., Takashima, H., & Boerkoel, C. F. (2010). Spinocerebellar ataxia with axonal neuropathy. Advances in Experimental Medicine and Biology, 685, 75–83. https://doi.org/10.1007/978-1-4419-6448-9_7
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