Spinocerebellar ataxia with axonal neuropathy

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

doi:10.1007/978-1-4419-6448-9_7

Spinocerebellar ataxia with axonal neuropathy

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

School of Biological Sciences

Research output: Contribution to journal › Article

Abstract / Description of output

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 language	English
Pages (from-to)	75-83
Number of pages	9
Journal	Advances in Experimental Medicine and Biology
Volume	685
DOIs	https://doi.org/10.1007/978-1-4419-6448-9_7
Publication status	Published - 2010

Keywords / Materials (for Non-textual outputs)

strand break
replication fork
spinocerebellar ataxia
premature ovarian failure
axonal neuropathy

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10.1007/978-1-4419-6448-9_7

Cite this

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title = "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.",

keywords = "strand break, replication fork, spinocerebellar ataxia, premature ovarian failure, axonal neuropathy",

author = "Cheryl Walton and Heidrun Interthal and Ryuki Hirano and Salih, {Mustafa A M} and Hiroshi Takashima and Boerkoel, {Cornelius F}",

year = "2010",

doi = "10.1007/978-1-4419-6448-9_7",

language = "English",

volume = "685",

pages = "75--83",

journal = "Advances in Experimental Medicine and Biology",

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T1 - Spinocerebellar ataxia with axonal neuropathy

AU - Walton, Cheryl

AU - Interthal, Heidrun

AU - Hirano, Ryuki

AU - Salih, Mustafa A M

AU - Takashima, Hiroshi

AU - Boerkoel, Cornelius F

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - strand break

KW - replication fork

KW - spinocerebellar ataxia

KW - premature ovarian failure

KW - axonal neuropathy

U2 - 10.1007/978-1-4419-6448-9_7

DO - 10.1007/978-1-4419-6448-9_7

M3 - Article

C2 - 20687496

SN - 0065-2598

VL - 685

SP - 75

EP - 83

JO - Advances in Experimental Medicine and Biology

JF - Advances in Experimental Medicine and Biology

ER -

Spinocerebellar ataxia with axonal neuropathy

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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