The mitochondrial DNA (mtDNA) of neural stem cells (NSCs) is vulnerable to oxidation damage. Subtle manipulations of the cellular redox state affect mtDNA integrity in addition to regulating the NSC differentiation lineage, suggesting a molecular link between mtDNA integrity and regulation of differentiation. Here we show that 8-oxoguanine DNA glycosylase (OGG1) is essential for repair of mtDNA...

Telomere integrity is critical for telomere function and genomic stability. We previously demonstrated that non-erythroid α-spectrin (αIISp) is present in mammalian cell nuclei where it is important in repair of DNA interstrand cross-links (ICLs) and chromosome stability. We now demonstrate that αIISp is also important for telomere maintenance after ICL damage. It localizes to telomeres in S ph...

BACKGROUND Chronic obstructive pulmonary disease (COPD) is characterised by oxidative stress and increased risk of lung carcinoma. Oxidative stress causes DNA damage which can be repaired by DNA-dependent protein kinase complex. OBJECTIVES To investigate DNA damage/repair balance and DNA-dependent protein kinase complex in COPD lung and in an animal model of smoking-induced lung damage and to...

Seckel Syndrome (SS) and Primary Microcephaly (MCPH) are disorders exhibiting marked microcephaly with a head circumference less than three standard deviations below the mean. ATR-Seckel Syndrome is conferred by mutations in ataxia and telangiectasia and Rad3 related (ATR), a kinase that activates a DNA damage signalling response. Cell lines from additional SS patients, who are normal for ATR, ...

Results are presented from cobalt-60 photon irradiations of multi-quantum well (MQW) modulators (to ~20Mrad) and optical fibres (to ~30Mrad). These components form part of the optical data-link for transfer of signals from the silicon microstrip and MSGC elements in CMS. Measurements of the reflectivity of the modulators at different bias voltages were made before and after irradiation showing ...

Optical data links are being developed at CERN for use in the tracking system of the Compact Muon Solenoid (CMS) experiment to be operated at the future CERN Large Hadron Collider. The radiation environment will be severe in the CMS tracker; simulations predict hadronic fluences >10/cm over an experimental lifetime of ten years, consisting of a mixture of neutrons, pions and protons over a wide...

1 Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Institute of Medical Sciences, Aberdeen, United Kingdom, 2 Mucosal & Salivary Biology Division, Dental Institute, King’s College London, United Kingdom, 3 Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, and Friedrich Schiller University, ...

DNA damage occurs in ischemia, excitotoxicity, inflammation, and other disorders that affect the central nervous system (CNS). Extensive DNA damage triggers cell death and in the mature CNS, this occurs primarily through activation of the poly(ADP-ribose) polymerase-1 (PARP-1) cell death pathway. PARP-1 is an abundant nuclear enzyme that, when activated by DNA damage, consumes nicotinamide aden...

SUMOylation plays important roles in the DNA damage response. However, whether it is important for interstrand crosslink repair remains unknown. We report that the SLX4 nuclease scaffold protein is regulated by SUMOylation. We have identified three SUMO interaction motifs (SIMs) in SLX4, mutating all of which abrogated the binding of SLX4 to SUMO-2 and covalent SLX4 SUMOylation. An SLX4 mutant ...

Several protein kinases from diverse eukaryotes known to perform important roles in DNA repair have also been shown to play critical roles in telomere maintenance. Here, we report that the human telomere-associated protein TRF2 is rapidly phosphorylated in response to DNA damage. We find that the phosphorylated form of TRF2 is not bound to telomeric DNA, as is the ground form of TRF2, and is ra...