The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin

Citation
Mc. Moreira et al., The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin, NAT GENET, 29(2), 2001, pp. 189-193
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
NATURE GENETICS
ISSN journal
1061-4036 → ACNP
Volume
29
Issue
2
Year of publication
2001
Pages
189 - 193
Database
ISI
SICI code
1061-4036(200110)29:2<189:TGMIAA>2.0.ZU;2-0
Abstract
The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920)(1-4) is the most frequent cause of autosomal recessive ataxia in Japan(2,4-9) and is s econd only to Friedreich ataxia in Portugal(10). It shares several neurolog ical features with ataxia-telanglectasia, including early onset ataxia, ocu lomotor apraxia and cerebellar atrophy, but does not share its extraneurolo gical features (immune deficiency, chromosomal instability and hypersensiti vity to X-rays). AOA1 is also characterized by axonal motor neuropathy(3,5, 9) and the later decrease of serum albumin levels and elevation of total ch olesterol(2,4,5,9). We have identified the gene causing AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new, ubiquitously ex pressed protein that we named aprataxin. This protein is composed of three domains that share distant homology with the amino-terminal domain of polyn ucleotide kinase 3'-phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is invo lved in DNA single-strand break repair (SSBR)(11) following exposure to ion izing radiation and reactive oxygen species. Fragile-HIT proteins (FHIT) cl eave diadenosine tetraphosphate, which is potentially produced during activ ation of the SSBR complex(12). The results suggest that aprataxin is a nucl ear protein with a role in DNA repair reminiscent of the function of the pr otein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.