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...

BACKGROUND In response to DNA double-strand breaks (DSBs), eukaryotic cells rapidly phosphorylate histone H2A isoform H2AX at a C-terminal serine (to form gamma-H2AX) and accumulate repair proteins at or near DSBs. To date, these events have been defined primarily at the resolution of light microscopes, and the relationship between gamma-H2AX formation and repair protein recruitment remains to ...

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...

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 ...

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...

Brostallicin is a DNA minor groove binder in phase II clinical trials. Here, we show that brostallicin induces gamma-H2AX nuclear foci that colocalize with 53BP1 and are dependent on glutathione, as shown by inhibition of those gamma-H2AX foci by l-buthionine sulfoximine. To differentiate brostallicin from the clinically approved minor groove binder trabectedin (ecteinascidin 743), we tested wh...

A very early step in the response of mammalian cells to DNA double-strand breaks is the phosphorylation of histone H2AX at serine 139 at the sites of DNA damage. Although the phosphatidylinositol 3-kinases, DNA-PK (DNA-dependent protein kinase), ATM (ataxia telangiectasia mutated), and ATR (ATM and Rad3-related), have all been implicated in H2AX phosphorylation, the specific kinase involved has...

Fanconi anemia (FA) is a chromosome fragility syndrome characterized by bone marrow failure and cancer susceptibility. The central FA protein FANCD2 is known to relocate to chromatin upon DNA damage in a poorly understood process. Here, we have induced subnuclear accumulation of DNA damage to prove that histone H2AX is a novel component of the FA/BRCA pathway in response to stalled replication ...