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Early-Onset Ataxia with Ocular Motor Apraxia and Hypoalbuminemia/Ataxia with Oculomotor Apraxia

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Diseases of DNA Repair

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 685))

Abstract

DNA single-strand breaks (SSBs) are non-overlapping discontinuities in strands of a DNA duplex. Significant attention has been given on the DNA SSB repair (SSBR) system in neurons, because the impairment of the SSBR causes human neurodegenerative disorders, including early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), also known as ataxia-oculomotor apraxia Type 1 (AOA1). EAOH/AOA1 is characterized by early-onset slowly progressive ataxia, ocular motor apraxia, peripheral neuropathy and hypoalbuminemia. Neuropathological examination reveals severe loss of Purkinje cells and moderate neuronal loss in the anterior horn and dorsal root ganglia. EAOH/AOA1 is caused by the mutation in the APTX gene encoding the aprataxin (APTX) protein. APTX interacts with X-ray repair cross-complementing group 1 protein, which is a scaffold protein in SSBR. In addition, APTX-defective cells show increased sensitivity to genotoxic agents, which result in SSBs. These results indicate an important role of APTX in SSBR. SSBs are usually accompanied by modified or damaged 5′- and 3′-ends at the break site. Because these modified or damaged ends are not suitable for DNA ligation, they need to be restored to conventional ends prior to subsequent repair processes. APTX restores the 5′-adenylate monophosphate, 3′-phosphates and 3′-phosphoglycolate ends. The loss of function of APTX results in the accumulation of SSBs, consequently leading to neuronal cell dysfunction and

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Authors and Affiliations

  1. Department of Neurology Clinical Neuroscience Branch Brain Research Institute, Niigata University, Niigata, Japan

    Masayoshi Tada, Akio Yokoseki & Tatsuya Sato

  2. Joetsu General Hospital, Niigata, Japan

    Takao Makifuchi

  3. Department of Molecular Neuroscience, Resource Branch for Brain Disease Research, Center for Bioresource-Based Research, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, 951-8122, Japan

    Osamu Onodera

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  1. Masayoshi Tada
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  2. Akio Yokoseki
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  3. Tatsuya Sato
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  4. Takao Makifuchi
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Correspondence to Osamu Onodera .

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  1. School of Science and Technology, Nottingham Trent University, Nottingham, UK

    Shamim I. Ahmad BSc, MSc, PhD

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Tada, M., Yokoseki, A., Sato, T., Makifuchi, T., Onodera, O. (2010). Early-Onset Ataxia with Ocular Motor Apraxia and Hypoalbuminemia/Ataxia with Oculomotor Apraxia. In: Ahmad, S.I. (eds) Diseases of DNA Repair. Advances in Experimental Medicine and Biology, vol 685. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6448-9_3

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