In the autoimmune syndrome rheumatoid arthritis (RA), T cells and T-cell precursors have age-inappropriate shortening of telomeres and accumulate deoxyribonucleic acid (DNA) double strand breaks. Whether damaged DNA elicits DNA repair activity and how this affects T-cell function and survival is unknown. Here, we report that naïve and resting T cells from RA patients are susceptible to undergo ...

During V(D)J recombination, the RAG proteins create DNA hairpins at the V, D, or J coding ends, and the structure-specific nuclease Artemis is essential to open these hairpins prior to joining. Artemis also is an endonuclease for 5' and 3' overhangs at many DNA double strand breaks caused by ionizing radiation, and Artemis functions as part of the nonhomologous DNA end joining pathway in repair...

Abstract Previous studies have shown that glioma stem-like cells (GSCs) evade conventional cytotoxic therapies and repopulate as recurrent tumors. A fuller understanding of the molecular mechanisms underlying biology therapy resistance GSCs is required. Our group has TAZ, a transcriptional co-factor highly expressed in about 70% glioblastomas (GBMs). TAZ its paralog YAP are oncogenic drivers br...

Herpes simplex virus type 1 (HSV-1) infection causes the active degradation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), and this process is reliant on the expression of the HSV-1 immediate-early protein Vmw110. In this study we investigated in more detail the mechanism by which the degradation occurs, the domains of Vmw110 which are required, and whether Vmw110 is by it...

The mechanisms of radiation-induced effects in cancer mainly involve double-strand breaks (DSBs) which are important in maintaining the stability of genes. The DNA repair genes breast cancer 1 (BRCA1) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are capable of maintaining genetic stability through two distinct and complementary repair mechanisms for DNA DSBs, known as repair-ho...

Several ring between ring fingers (RBR) -domain proteins, such as Parkin and Parc, have been shown to be E3 ligases involved in important biological processes. Here, we identify a poorly characterized RBR protein, Ring Finger protein 144A (RNF144A), as the first, to our knowledge, mammalian E3 ubiquitin ligase for DNA-PKcs. We show that DNA damage induces RNF144A expression in a p53-dependent m...

The Ku protein is a complex of two subunits, Ku70 and Ku80. Ku plays an important role in DNA-PKcs-dependent double-strand break repair and V(D)J recombination, and in growth regulation, which is DNA-PKcs-independent. We studied the expression and the subcellular localization of Ku and DNA-PKcs throughout the cell cycle in several established human cell lines. Using immunofluorescence analysis ...

DNA double-strand breaks (DSBs) can be repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). In vertebrates, the first step in NHEJ is recruitment of the DNA-dependent protein kinase (DNA-PK) to DNA termini. DNA-PK consists of a catalytic subunit (DNA-PKcs) that is recruited to DNA ends by the Ku70/Ku80 heterodimer. Although Ku has been identified in a wide varie...

Introduction Protein kinase C (PKC) is a family of phospholipiddependent serine-threonine kinases that regulate cell growth and differentiation (reviewed in [ 1 4 ) . PKC is also the major intracellular receptor for tumour-promoting phorbol esters [ 1-31. Molecular cloning and biochemical separation of the individual gene products has led to a classification system for the PKC isoenzymes based ...

In this study, we evaluated the role of tumor cell and tumor stroma sensitivity as determinants of radiation-induced tumor growth delay. A DNA double-strand break repair-defective DNA-PKcs(-/-) tumor cell line and its radioresistant DNA-PKcs(+/+)-transfected counterpart were used to initiate tumors in nude and hypersensitive severe combined immunodeficient (SCID) mice. Insertion of the human DN...