Abstract：
:The tumour-suppressor gene ATM, mutations in which cause the human genetic disease ataxia telangiectasia (A-T), encodes a key protein kinase that controls the cellular response to DNA double-strand breaks (DSBs). DNA DSBs caused by ionizing radiation or chemicals result in rapid ATM autophosphorylation, leading to checkpoint activation and phosphorylation of substrates that regulate cell-cycle progression, DNA repair, transcription and cell death. However, the precise mechanism by which damaged DNA induces ATM and checkpoint activation remains unclear. Here, we demonstrate that linear DNA fragments added to Xenopus egg extracts mimic DSBs in genomic DNA and provide a platform for ATM autophosphorylation and activation. ATM autophosphorylation and phosphorylation of its substrate NBS1 are dependent on DNA fragment length and the concentration of DNA ends. The minimal DNA length required for efficient ATM autophosphorylation is approximately 200 base pairs, with cooperative autophosphorylation induced by DNA fragments of at least 400 base pairs. Importantly, full ATM activation requires it to bind to DNA regions flanking DSB ends. These findings reveal a direct role for DNA flanking DSB ends in ATM activation.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
You Z,Bailis JM,Johnson SA,Dilworth SM,Hunter Tdoi
10.1038/ncb1651subject
Has Abstractpub_date
2007-11-01 00:00:00pages
1311-8issue
11eissn
1465-7392issn
1476-4679pii
ncb1651journal_volume
9pub_type
杂志文章abstract：:Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewir...
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更新日期：2007-04-01 00:00:00
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