Synthesis of trimetallic iron-boron core and gold shell nanoparticles for experimental cancer radiotherapy.

Cancer is a significant and constantly growing clinical problem all over the word. For many types of cancer there has been little change in mortality rate of CRC in the past decades and treatment options are limited. A striking example is malignant Glioblastoma (GBM) which exhibits a high degree of infiltration of surrounding healthy brain tissue, extremely high mortality rate, morbidity and most life-years lost of any cancer.

Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration.

DNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double-strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DNA damage response might be neuroprotective.

Ku70 N-terminal lysines acetylation/deacetylation is required for radiation-induced DNA-double strand breaks repair.

Ku70 protein in hetero-trimeric complex with Ku80 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) represents a critical component of the nonhomologous-end-joining (NHEJ), the major machinery of DSBs repair in mammalian cells. It has been previously shown that modulation of Ku70 acetylation by histone deacetylases (HDAC) inhibitors induced sensitization of cancer cells to chemotherapeutic agents. However, the effects of such modulation on the repair of Ionizing Radiation (IR)-induced DSBs and the importance of dynamic equilibrium of acetylation/deacetylation have not been studied in details.

Mutations in the NHEJ component XRCC4 cause primordial dwarfism.

Non-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive immune system. In contrast, we have recently found that biallelic mutations in LIG4 are a common cause of microcephalic primordial dwarfism (MPD), a phenotype characterized by prenatal-onset extreme global growth failure.