Pilch Duane R, Sedelnikova Olga A, Redon Christophe, Celeste Arkady, Nussenzweig Andre, Bonner William M
Laboratory of Molecular Pharmacology, National Cancer Institute, National Insitutes of Health, Bethesda, MD 20892, USA.
Biochem Cell Biol. 2003 Jun;81(3):123-9. doi: 10.1139/o03-042.
Phosphorylated H2AX (gamma-H2AX) is essential to the efficient recognition and (or) repair of DNA double strand breaks (DSBs), and many molecules, often thousands, of H2AX become rapidly phosphorylated at the site of each nascent DSB. An antibody to gamma-H2AX reveals that this highly amplified process generates nuclear foci. The phosphorylation site is a serine four residues from the C-terminus which has been evolutionarily conserved in organisms from giardia intestinalis to humans. Mice and yeast lacking the conserved serine residue demonstrate a variety of defects in DNA DSB processing. H2AX Delta/Delta mice are smaller, sensitive to ionizing radiation, defective in class switch recombination and spermatogenesis while cells from the mice demonstrate substantially increased numbers of genomic defects. gamma-H2AX foci formation is a sensitive biological dosimeter and presents new and exciting opportunities to understand important biological processes, human diseases, and individual variations in radiation sensitivity. These potentialities demonstrate the importance of understanding the parameters and functions of gamma-H2AX formation.
磷酸化的H2AX（γ-H2AX）对于高效识别和（或）修复DNA双链断裂（DSB）至关重要，并且在每个新生DSB位点，通常有数千个H2AX分子会迅速发生磷酸化。针对γ-H2AX的抗体显示，这种高度放大的过程会产生核灶。磷酸化位点是C末端的第四个丝氨酸残基，该位点在从肠道贾第虫到人类的生物体中具有进化保守性。缺乏保守丝氨酸残基的小鼠和酵母在DNA DSB处理中表现出多种缺陷。H2AX Delta/Delta小鼠体型较小，对电离辐射敏感，在类别转换重组和精子发生方面存在缺陷，而来自这些小鼠的细胞显示出大量增加的基因组缺陷。γ-H2AX灶形成是一种敏感的生物剂量计，为理解重要的生物学过程、人类疾病以及辐射敏感性的个体差异提供了新的、令人兴奋的机会。这些潜力证明了理解γ-H2AX形成的参数和功能的重要性。
