Abstract：
: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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Fernandez-Capetillo O,Chen HT,Celeste A,Ward I,Romanienko PJ,Morales JC,Naka K,Xia Z,Camerini-Otero RD,Motoyama N,Carpenter PB,Bonner WM,Chen J,Nussenzweig Adoi
10.1038/ncb884keywords:
subject
Has Abstractpub_date
2002-12-01 00:00:00pages
993-7issue
12eissn
1465-7392issn
1476-4679pii
ncb884journal_volume
4pub_type
杂志文章abstract：:Cellular senescence is a stable proliferation arrest induced by triggers such as short telomeres, activated oncogenes and genotoxic stress. Two studies show that cellular senescence induced by genotoxic stress depends on chronic DNA-damage signalling from irreparable damage to telomeres. Hence, dysfunctional or damage...
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pub_type： 评论,新闻
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更新日期：2017-08-31 00:00:00
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更新日期：2014-10-01 00:00:00
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更新日期：2016-12-23 00:00:00
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更新日期：2015-03-01 00:00:00
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更新日期：2017-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：2007-07-01 00:00:00
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更新日期：2016-07-27 00:00:00
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pub_type： 杂志文章
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更新日期：2009-07-01 00:00:00
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更新日期：2008-11-01 00:00:00
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更新日期：2016-11-01 00:00:00
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更新日期：2009-03-01 00:00:00
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更新日期：2007-06-01 00:00:00
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更新日期：2010-05-01 00:00:00
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更新日期：2020-04-01 00:00:00
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pub_type： 评论,杂志文章
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更新日期：2008-10-01 00:00:00
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更新日期：2020-05-01 00:00:00
