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rdf:type |
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lifeskim:mentions |
umls-concept:C0004135,
umls-concept:C0012854,
umls-concept:C0026882,
umls-concept:C0031715,
umls-concept:C0033684,
umls-concept:C0127400,
umls-concept:C0216510,
umls-concept:C1332120,
umls-concept:C1336660,
umls-concept:C1336767,
umls-concept:C1363844,
umls-concept:C1515877,
umls-concept:C1751194,
umls-concept:C1879547
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pubmed:issue |
22
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pubmed:dateCreated |
2011-5-30
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pubmed:abstractText |
The ataxia-telangiectasia mutated and RAD3-related (ATR) kinase initiates DNA damage signaling pathways in human cells after DNA damage such as that induced upon exposure to ultraviolet light by phosphorylating many effector proteins including the checkpoint kinase Chk1. The conventional view of ATR activation involves a universal signal consisting of genomic regions of replication protein A-covered single-stranded DNA. However, there are some indications that the ATR-mediated checkpoint can be activated by other mechanisms. Here, using the well defined Escherichia coli lac repressor/operator system, we have found that directly tethering the ATR activator topoisomerase II?-binding protein 1 (TopBP1) to DNA is sufficient to induce ATR phosphorylation of Chk1 in an in vitro system as well as in vivo in mammalian cells. In addition, we find synergistic activation of ATR phosphorylation of Chk1 when the mediator protein Claspin is also tethered to the DNA with TopBP1. Together, these findings indicate that crowding of checkpoint mediator proteins on DNA is sufficient to activate the ATR kinase.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Atr protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/CLSPN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Checkpoint kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Single-Stranded,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TOPBP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Topbp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ataxia telangiectasia mutated...,
http://linkedlifedata.com/resource/pubmed/chemical/claspin protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1083-351X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
3
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19229-36
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:21502314-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:21502314-Animals,
pubmed-meshheading:21502314-Carrier Proteins,
pubmed-meshheading:21502314-Cell Cycle Proteins,
pubmed-meshheading:21502314-DNA, Single-Stranded,
pubmed-meshheading:21502314-DNA Damage,
pubmed-meshheading:21502314-DNA-Binding Proteins,
pubmed-meshheading:21502314-Enzyme Activation,
pubmed-meshheading:21502314-Escherichia coli,
pubmed-meshheading:21502314-Humans,
pubmed-meshheading:21502314-Mice,
pubmed-meshheading:21502314-NIH 3T3 Cells,
pubmed-meshheading:21502314-Nuclear Proteins,
pubmed-meshheading:21502314-Phosphorylation,
pubmed-meshheading:21502314-Protein Kinases,
pubmed-meshheading:21502314-Protein-Serine-Threonine Kinases,
pubmed-meshheading:21502314-Recombinant Proteins,
pubmed-meshheading:21502314-Tumor Suppressor Proteins
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pubmed:year |
2011
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pubmed:articleTitle |
Tethering DNA damage checkpoint mediator proteins topoisomerase IIbeta-binding protein 1 (TopBP1) and Claspin to DNA activates ataxia-telangiectasia mutated and RAD3-related (ATR) phosphorylation of checkpoint kinase 1 (Chk1).
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pubmed:affiliation |
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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