Poly-ADP ribose polymerase 1 (PARP-1) is a protein well described as a sensor for single strand DNA breaks (SSB) [1]. After its activation a localized poly(ADPribosyl)ation of proteins near the DNA breaks is initiated, which is necessary for efficient binding of other repair proteins like XRCC1. The aprataxin protein has interaction domains for both SSB-repair proteins such as PARP1 and XRCC1 a...

Hereditary ataxias are a clinically and genetically heterogeneous family of disorders defined by the inability to control gait and muscle coordination. Given the nonspecific symptoms of many hereditary ataxias, precise diagnosis relies on molecular genetic testing. To this end, we conducted whole-exome sequencing (WES) on a large consanguineous Iranian family with hereditary ataxia and oculomot...

Aprataxin, aprataxin and PNKP-like factor (APLF) and polynucleotide kinase phosphatase (PNKP) are key DNA-repair proteins with diverse functions but which all contain a homologous forkhead-associated (FHA) domain. Their primary binding targets are casein kinase 2-phosphorylated forms of the XRCC1 and XRCC4 scaffold molecules which respectively coordinate single-stranded and double-stranded DNA ...

Ataxia-oculomotor apraxia 1 (AOA1) is an autosomal recessive neurodegenerative disease that is reminiscent of ataxia-telangiectasia (A-T). AOA1 is caused by mutations in the gene encoding aprataxin, a protein whose physiological function is currently unknown. We report here that, in contrast to A-T, AOA1 cell lines exhibit neither radioresistant DNA synthesis nor a reduced ability to phosphoryl...

OBJECTIVES/BACKGROUND Ataxia with oculomotor apraxia defines a group of genetically distinct recessive ataxias including ataxia-telangectasia (A-T, ATM gene), ataxia with oculomotor apraxia type 1 (AOA1, APTX gene) and type 2 (AOA2, SETX gene). Although, a few unique clinical features differentiate each of these forms, the patients also share common clinical signs, such as the presence of cereb...

Ataxia telangiectasia (ATM), AT like disorder (MRE11), AOA1 (APTX) and AOA2 (SETX) in the UK – variability of the neurological, genetic and cellular phenotypes 19.05-20.00 Jan Hoeijmakers (Netherlands) The link between DNA damage, global and transcription coupled repair and neurodegeneration Mark O'Driscoll (UK) Defective genome stability and impaired neurogenesis in congenital human disorders ...

Short-patch repair of DNA single-strand breaks and gaps (SSB) is coordinated by XRCC1, a scaffold protein that recruits the DNA polymerase and DNA ligase required for filling and sealing the damaged strand. XRCC1 can also recruit end-processing enzymes, such as PNK (polynucleotide kinase 3'-phosphatase), Aprataxin and APLF (aprataxin/PNK-like factor), which ensure the availability of a free 3'-...

Three experiments examined whether famous faces would be affected by the age at which knowledge of the face was first acquired (AoA). Using a multiple regression design, Experiment 1 showed that rated familiarity and AoA were significant predictors of the time required to name pictures of celebrities' faces and the accuracy of producing their names. Experiment 2 replicated an effect of AoA usin...