2026-07-24T06:21:33Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/177032024-11-29T13:59:37Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Fernandez-Capetillo, Oscar author Chen, Hua-Tang author Celeste, Arkady author Ward, Irene author Romanienko, Peter J author Morales, Julio C author Naka, Kazuhito author Xia, Zhenfang author Camerini-Otero, R Daniel author Motoyama, Noboru author Carpenter, Phillip B author Bonner, William M author Chen, Junjie author Nussenzweig, André author 2002-12 Activation 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. Nat Cell Biol . 2002;4(12):993-7. 10.1038/ncb884 1465-7392 Nature cell biology 12447390 http://hdl.handle.net/20.500.12105/17703 DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1.