Podhorecka Monika
Klinika Hematoonkologii i Transplantacji Szpiku, Uniwersytet Medyczny w Lublinie, Poland.
Postepy Hig Med Dosw (Online). 2009 Feb 27;63:92-8.
Double-strand breaks (DSBs) are highly deleterious DNA lesions because they can lead to chromosome aberrations or apoptosis. Various physical, chemical, and biological factors are involved in DSB induction. The formation of nuclear DSBs triggers phosphorylation of H2AX at Ser139; phosphorylated H2AX is named gamma H2AX. It is believed that histone H2AX phosphorylation is required for the concentration of DNA repair proteins to the damaged chromatin. H2AX is phosphorylated by members of phosphoinositide 3-kinase-related protein kinases (PIKKs), such as ATM (ataxia teleangiectasia mutated), which is the main mediator of H2AX phosphorylation in response to DSB induction. The development of immunocytochemical methods of gamma H2AX detection provided a convenient tool for research and is considered a gold standard for DSB analysis. These methods are sensitive and specific in the detection of a single DSB. Assessment of H2AX phosphorylation can be used in clinical practice as a marker of premalignant lesions and to predict cell sensitivity to radiotherapy and chemotherapy.
双链断裂(DSBs)是极具危害性的DNA损伤,因为它们可导致染色体畸变或细胞凋亡。多种物理、化学和生物因素都参与了DSB的诱导。细胞核DSB的形成会触发H2AX在丝氨酸139处的磷酸化;磷酸化的H2AX被称为γH2AX。据信,组蛋白H2AX磷酸化是DNA修复蛋白聚集到受损染色质所必需的。H2AX由磷酸肌醇3激酶相关蛋白激酶(PIKKs)家族成员磷酸化,如共济失调毛细血管扩张症突变基因(ATM),它是响应DSB诱导时H2AX磷酸化的主要介导因子。γH2AX检测免疫细胞化学方法的发展为研究提供了便利工具,被认为是DSB分析的金标准。这些方法在检测单个DSB时灵敏且特异。H2AX磷酸化的评估可在临床实践中用作癌前病变的标志物,并预测细胞对放疗和化疗的敏感性。