Phosphorylation of Histone H2AX and Activation of Mre11, Rad50, and Nbs1 in Response to Replication-dependent DNA Double-strand Breaks Induced by Mammalian DNA Topoisomerase I Cleavage Complexes

Furuta, Takahisa; Takemura, Haruyuki; Liao, Zhi-Yong; Aune, Gregory J.; Redon, Christophe; Sedelnikova, Olga A.; Pilch, Duane R.; Rogakou, Emmy P.; Celeste, Arkady; Chen, Hua Tang; Nussenzweig, Andre; Aladjem, Mirit I.; Bonner, William M.; Pommier, Yves

doi:10.1074/jbc.m300198200

Phosphorylation of Histone H2AX and Activation of Mre11, Rad50, and Nbs1 in Response to Replication-dependent DNA Double-strand Breaks Induced by Mammalian DNA Topoisomerase I Cleavage Complexes

DNA double-strand breaks originating from diverse causes in eukaryotic cells are accompanied by the formation of phosphorylated H2AX (γH2AX) foci. Here we show that γH2AX formation is also a cellular response to topoisomerase I cleavage complexes known to induce DNA double-strand breaks during re…