Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139
Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139
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DOI：
10.1074/jbc.275.13.9390
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发表时间：
2000-03-31
影响因子：
4.8
通讯作者：
Bonner, WM
中科院分区：
文献类型：
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作者：
Rogakou, EP;Nieves-Neira, W;Bonner, WM
组蛋白H2 AX是H2 A组蛋白家族中普遍存在的成员，其与其他H2 A组蛋白的不同之处在于存在进化上保守的C-末端基序-KKATQASQEY。当DNA双链断裂通过各种物理和化学手段引入细胞和动物的染色质中时，该基序中的丝氨酸残基在细胞和动物中迅速磷酸化。在目前的通信中，我们表明，这种磷酸化形式的H2 AX，称为γ-H2 AX，出现在细胞凋亡过程中同时出现的高分子量DNA片段的初始外观。γ-H2 AX在核小体间DNA片段出现和磷脂酰丝氨酸外化到外膜小叶之前形成。γ-H2 AX的形成被N-苄氧羰基-Val-AlaAsp-氟甲基酮和半胱天冬酶激活的DNA酶的抑制剂抑制，并且当DNA酶I和限制性酶被引入细胞中时，γ-H2 AX的形成被诱导，这表明任何凋亡核酸内切酶都足以诱导γ-H2 AX的形成。这些结果表明，γ-H2 AX形成是细胞凋亡期间DNA片段化起始后的早期染色质修饰。
Histone H2AX is a ubiquitous member of the H2A histone family that differs from the other H2A histones by the presence of an evolutionarily conserved C-terminal motif, -KKATQASQEY. The serine residue in this motif becomes rapidly phosphorylated in cells and animals when DNA double-stranded breaks are introduced into their chromatin by various physical and chemical means. In the present communication we show that this phosphorylated form of H2AX, referred to as gamma-H2AX, appears during apoptosis concurrently with the initial appearance of high molecular weight DNA fragments. gamma-H2AX forms before the appearance of internucleosomal DNA fragments and the externalization of phosphatidylserine to the outer membrane leaflet. gamma-H2AX formation is inhibited by N-benzyloxycarbonyl-Val-AlaAsp-fluoromethyl ketone and the inhibitor of caspase-activated DNase, and it is induced when DNase I and restriction enzymes are introduced into cells, suggesting that any apoptotic endonuclease is sufficient to induce gamma-H2AX formation. These results indicate that gamma-H2AX formation is an early chromatin modification following initiation of DNA fragmentation during apoptosis.