Precise regulation of DNA damage response is crucial for cellular survival after DNA damage, and its abrogation often results in genomic instability in cancer. Phosphorylated histone H2AX (γH2AX) forms nuclear foci at sites of DNA damage and facilitates DNA damage response and repair. MicroRNAs (miRNA) are short, nonprotein-encoding RNA molecules, which posttranscriptionally regulate gene expre...

During the last decade, chromatin research has been focusing on the role of histone variability as a modulator of chromatin structure and function. Histone variability can be the result of either post-translational modifications or intrinsic variation at the primary structure level: histone variants. In this review, we center our attention on one of the most extensively characterized of such hi...

A comprehensive genome-wide screen of radiosensitization targets in HeLa cells was performed using a shRNA-library/functional cluster analysis and DNMT3B was identified as a candidate target. DNMT3B RNAi increased the sensitivity of HeLa, A549 and HCT116 cells to both γ-irradiation and carbon-ion beam irradiation. DNMT3B RNAi reduced the activation of DNA damage responses induced by γ-irradiati...

Mammalian ATR and ATM checkpoint kinases modulate chromatin structures near DNA breaks by phosphorylating a serine residue in the carboxy-terminal tail SQE motif of histone H2AX. Histone H2A is similarly regulated in Saccharomyces cerevisiae. The phosphorylated forms of H2AX and H2A, known as gamma-H2AX and gamma-H2A, are thought to be important for DNA repair, although their evolutionarily con...

Matrix metalloproteinase (MMP)-1 promotes ultraviolet (UV)-triggered long-term detrimental effects such as cancer formation and premature skin aging. Although histone modifications may play a crucial role in the transcriptional regulation of MMP-1, the relationship between UV-induced histone modification and MMP-1 expression is not completely understood. Here, we identify regulators of histone ...

Interstrand cross-links (ICLs) are an extremely toxic class of DNA damage incurred during normal metabolism or cancer chemotherapy. ICLs covalently tether both strands of duplex DNA, preventing the strand unwinding that is essential for polymerase access. The mechanism of ICL repair in mammalian cells is poorly understood. However, genetic data implicate the Ercc1-Xpf endonuclease and proteins ...

In radiotherapy, in vivo measurement of dose distribution within patients' lymphocytes can be performed by detecting gamma-H2AX foci in lymphocyte nuclei. This method can help in determining the whole-body dose. Options for risk estimations for toxicities in normal tissue and for the incidence of secondary malignancy are still under debate. In this investigation, helical tomotherapy (TOMO) is c...

The resection of broken DNA ends is required for DNA double-strand break (DSB) repair by homologous recombination (HR) but can inhibit normal repair by nonhomologous end joining (NHEJ), the main DSB repair pathway in G1-phase cells. Antigen receptor gene assembly proceeds through DNA DSB intermediates generated in G1-phase lymphocytes by the RAG endonuclease. These DSBs activate ATM, which phos...

The ATM protein kinase mediates a rapid induction of cellular responses to DNA double strand breaks (DSBs). ATM kinase activity is enhanced immediately after exposure of cells to DSB-inducing agents, but no changes in its amount or subcellular location following that activation have been reported. We speculated that some of the ATM molecules associate with sites of DSBs, while the rest of the n...

In the last decade, many papers highlighted that the histone variant H2AX and its phosphorylation on Ser 139 (γH2AX) cannot be simply considered a specific DNA double-strand-break (DSB) marker with a role restricted to the DNA damage response, but rather as a 'protagonist' in different scenarios. This review will present and discuss an up-to-date view regarding the 'non-canonical' H2AX roles, f...