Eukaryotic circadian clocks are built on transcriptional feedback loops. In mammals, the PERIOD (PER) and CRYPTOCHROME (CRY) proteins accumulate, form a large nuclear complex (PER complex), and repress their own transcription. We found that mouse PER complexes included RNA helicases DDX5 and DHX9, active RNA polymerase II large subunit, Per and Cry pre-mRNAs, and SETX, a helicase that promotes ...

Rad26, a DNA dependent ATPase that is homologous to human CSB, has been well known to play an important role in transcription coupled DNA repair (TCR) in the yeast Saccharomyces cerevisiae Sen1, a DNA/RNA helicase that is essential for yeast cell viability and homologous to human senataxin, has been known to be required for transcriptional termination of short noncoding RNA genes and for a fail...

A 23-year-old woman had presented initially to a podiatrist complaining of poorly fitting shoes during her adolescence. After extensive neurological review, she was diagnosed with ataxia with oculomotor apraxia type 2. This is a progressive autosomal recessive ataxia associated with cerebellar atrophy, peripheral neuropathy and an elevated serum α-fetoprotein. Within Europe, it is the most freq...

Inherited peripheral neuropathies (IPNs) are a group of related diseases primarily affecting the peripheral motor and sensory neurons. They include the hereditary sensory neuropathies (HSN), hereditary motor neuropathies (HMN), and Charcot-Marie-Tooth disease (CMT). Using whole-exome sequencing (WES) to achieve a genetic diagnosis is particularly suited to IPNs, where over 80 genes are involved...

R-loops are cellular structures composed of an RNA/DNA hybrid, which is formed when the RNA hybridises to a complementary DNA strand and a displaced single-stranded DNA. R-loops have been detected in various organisms from bacteria to mammals and play crucial roles in regulating gene expression, DNA and histone modifications, immunoglobulin class switch recombination, DNA replication, and genom...

Juvenile onset amyotrophic lateral sclerosis (ALS) is a very rare form of motor neuron disease, with the first symptoms of motor neuron degeneration manifested before 25 years of age. Juvenile ALS is more frequently familial in nature than the adult-onset forms. Mutations in the alsin (ALS2), senataxin (SETX), and Spatacsin (SPG11) have been associated with familial ALS with juvenile onset and ...

OBJECTIVE To determine whether GGGGCC (G4C2) repeat expansions at loci other than C9orf72 serve as common causes of amyotrophic lateral sclerosis (ALS). METHODS We assessed G4C2 repeat number in 28 genes near known ALS and frontotemporal dementia (FTD) loci by repeat-primed PCR coupled with fluorescent fragment analysis in 199 patients with ALS (17 familial, 182 sporadic) and 136 healthy cont...

Consider a game in a given set of intervals (and their implied interval graph G) in which the adversary chooses an independent setX in G. The goal is to discover this hidden independent set X by making the fewest queries of the form “Is point p covered by an interval inX?” Our interest in this problem stems from two applications: experimental gene discovery with PCR technology and the game of B...

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 ...