Linked Life Data

17478428

Source:http://linkedlifedata.com/resource/pubmed/id/17478428

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pubmed-article:17478428pubmed:abstractTextATM (ataxia telangiectasia-mutated) and ATR (ATM-Rad3-related) are proximal checkpoint kinases that regulate DNA damage response (DDR). Identification and characterization of ATM/ATR substrates hold the keys for the understanding of DDR. Few techniques are available to identify protein kinase substrates. Here, we screened for potential ATM/ATR substrates using phospho-specific antibodies against known ATM/ATR substrates. We identified proteins cross-reacting to phospho-specific antibodies in response to DNA damage by mass spectrometry. We validated a subset of the candidate substrates to be phosphorylated in an ATM/ATR-dependent manner in vivo. Combining with a functional checkpoint screen, we identified proteins that belong to the ubiquitin-proteasome system (UPS) to be required in mammalian DNA damage checkpoint control, particularly the G(1) cell cycle checkpoint, thus revealing protein ubiquitylation as an important regulatory mechanism downstream of ATM/ATR activation for checkpoint control.lld:pubmed
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pubmed-article:17478428pubmed:articleTitleA proteomic analysis of ataxia telangiectasia-mutated (ATM)/ATM-Rad3-related (ATR) substrates identifies the ubiquitin-proteasome system as a regulator for DNA damage checkpoints.lld:pubmed
pubmed-article:17478428pubmed:affiliationVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.lld:pubmed
pubmed-article:17478428pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:17478428pubmed:publicationTypeResearch Support, U.S. Gov't, Non-P.H.S.lld:pubmed
pubmed-article:17478428pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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