BACKGROUND In response to DNA double-strand breaks, the histone protein H2AX becomes phosphorylated at its C-terminal serine 139 residue, referred to as γ-H2AX. Formation of γ-H2AX foci is associated with recruitment of p53-binding protein 1 (53BP1), a regulator of the cellular response to DNA double-strand breaks. γ-H2AX expression in peripheral blood mononuclear cells (PBMCs) was recently pro...

Changes in chromatin structure induced by posttranslational modifications of histones are important regulators of genomic function. Phosphorylation of histone H2AX promotes DNA repair and helps maintain genomic stability. Although B cells lacking H2AX show impaired class switch recombination (CSR), the precise role of H2AX in CSR and somatic hypermutation (SHM) has not been defined. We show tha...

BACKGROUND Phosphorylated histone H2AX ( γ -H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ -H2AX in hepatocellular carcinoma (HCC), we measured the level of γ -H2AX in HCC, dysplastic nodule, and nontumorous liver diseases. METHODS The level of γ -H2AX was measured by immunohistochemistry in fifty-eight HCC,...

Histone H2AX is required to maintain genomic stability in cells and to suppress malignant transformation of lymphocytes in mice. H2ax(-/-)p53(-/-) mice succumb predominantly to immature alphabeta T-cell lymphomas with translocations, deletions, and genomic amplifications that do not involve T-cell receptor (TCR). In addition, H2ax(-/-)p53(-/-) mice also develop at lower frequencies B and T lymp...

During meiosis, phosphorylation of H2AX is one of the earliest cellular responses to the generation of DNA double-strand breaks (DSBs) by the SPO11 topoisomerase. ATM is the kinase which mediates the formation of phosphorylated H2AX (H2AX) meiotic foci, while ATR is the kinase which signals chromosome asynapsis at the level of the XY bivalent. To investigate the possible role of ATR also in DN...

Abstract Diabetic cardiomyopathy increases the risk of heart failure and worsens prognosis for diabetes mellitus (DM) patients. Its development depends on many factors, including modification nitric oxide production impaired DNA repair. The goal present work was to study in vivo effects a 1,4-dihydropyridine AV-153, known as antimutagen DNA-binder, integrity, expression several proteins involve...

The histone H2A variant H2AX is phosphorylated in response to DNA double-strand breaks originating from diverse origins, including dysfunctional telomeres. Here, we show that normal mitotic telomere maintenance does not require H2AX. Moreover, H2AX is dispensable for the chromosome fusions arising from either critically shortened or deprotected telomeres. However, H2AX has an essential role in ...

Introduction: Radiation-induced bystander effect (RIBE) is a well-known response associated with the induction of radiation effects in non-irradiated cells via signaling of hit ones. As this so-called phenomenon has been largely investigated in low dose levels, few studies focused on higher dose levels such as grid therapy. Grid therapy or spatially fractionated gri...

is phosphorylated and forms discrete foci immediately (within 5 min) after irradiation [5]; hence, it may represent an earlier signaling response than formation of the complex within 2 hr of irradiation, as detected by anti-hMRE11 antibody (Figure 2A). In the absence of NBS1, 5 Medical and Biological Laboratories Nagano 396-0002 hMRE11 protein was confined to the cytoplasm and did not form nucl...

Proper deposition and activation of Aurora B at the centromere is critical for faithful chromosome segregation in mammals. However, the mechanistic basis for abrupt Aurora B kinase activation at the centromere has not yet been fully understood. We demonstrate here that Aurora B-mediated phosphorylation of histone H2AX at serine 121 (H2AX-pS121) promotes Aurora B autophosphorylation and is essen...