Fernandez-Capetillo, OscarChen, Hua-TangCeleste, ArkadyWard, IreneRomanienko, Peter JMorales, Julio CNaka, KazuhitoXia, ZhenfangCamerini-Otero, R DanielMotoyama, NoboruCarpenter, Phillip BBonner, William MChen, JunjieNussenzweig, André2024-02-092024-02-092002-12Nat Cell Biol . 2002;4(12):993-7.1465-7392http://hdl.handle.net/20.500.12105/17703Activation of the ataxia telangiectasia mutated (ATM) kinase triggers diverse cellular responses to ionizing radiation (IR), including the initiation of cell cycle checkpoints. Histone H2AX, p53 binding-protein 1 (53BP1) and Chk2 are targets of ATM-mediated phosphorylation, but little is known about their roles in signalling the presence of DNA damage. Here, we show that mice lacking either H2AX or 53BP1, but not Chk2, manifest a G2-M checkpoint defect close to that observed in ATM(-/-) cells after exposure to low, but not high, doses of IR. Moreover, H2AX regulates the ability of 53BP1 to efficiently accumulate into IR-induced foci. We propose that at threshold levels of DNA damage, H2AX-mediated concentration of 53BP1 at double-strand breaks is essential for the amplification of signals that might otherwise be insufficient to prevent entry of damaged cells into mitosis.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internacional1244739041299310.1038/ncb884Nature cell biologyopen access