Source:http://linkedlifedata.com/resource/pubmed/id/15279810
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8-9
|
| pubmed:dateCreated |
2004-7-28
|
| pubmed:abstractText |
Comparison of the clinical and cellular phenotypes of different genomic instability syndromes provides new insights into functional links in the complex network of the DNA damage response. A prominent example of this principle is provided by examination of three such disorders: ataxia-telangiectasia (A-T) caused by lack or inactivation of the ATM protein kinase, which mobilises the cellular response to double strand breaks in the DNA; ataxia-telangiectasia-like disease (ATLD), a result of deficiency of the human Mre11 protein; and the Nijmegen breakage syndrome (NBS), which represents defective Nbs1 protein. Mre11 and Nbs1 are members of the Mre11/Rad50/Nbs1 (MRN) protein complex. MRN and its individual components are involved in different responses to cellular damage induced by ionising radiation and radiomimetic chemicals, including complexing with chromatin and with other damage response proteins, formation of radiation-induced foci, and the induction of different cell cycle checkpoints. The phosphorylation of Nbs1 by ATM would indicate that ATM acts upstream of the MRN complex. Consistent with this were the suggestions that ATM could be activated in the absence of fully functional Nbs1 protein. In contrast, the regulation of some ATM target proteins, e.g. Smc1 requires the MRN complex as well as ATM. Nbs1 may, therefore, be both a substrate for ATM and a mediator of ATM function. Recent studies that indicate a requirement of the MRN complex for proper ATM activation suggest that the relationship between ATM and the MRN complex in the DNA damage response is yet to be fully determined. Despite the fact that both Mre11 and Nbs1 are part of the same MRN complex, deficiency in either protein in humans does not lead to the same clinical picture. This suggests that components of the complex may also act separately.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Chromosomal Proteins, Non-Histone,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/H2AFX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/MRE11A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NBN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ataxia telangiectasia mutated...,
http://linkedlifedata.com/resource/pubmed/chemical/structural maintenance of...
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
1568-7864
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
3
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1219-25
|
| pubmed:dateRevised |
2011-11-2
|
| pubmed:meshHeading |
pubmed-meshheading:15279810-Alleles,
pubmed-meshheading:15279810-Ataxia Telangiectasia,
pubmed-meshheading:15279810-Cell Cycle,
pubmed-meshheading:15279810-Cell Cycle Proteins,
pubmed-meshheading:15279810-Chromatin,
pubmed-meshheading:15279810-Chromosomal Proteins, Non-Histone,
pubmed-meshheading:15279810-DNA Damage,
pubmed-meshheading:15279810-DNA-Binding Proteins,
pubmed-meshheading:15279810-Histones,
pubmed-meshheading:15279810-Humans,
pubmed-meshheading:15279810-Models, Genetic,
pubmed-meshheading:15279810-Mutation,
pubmed-meshheading:15279810-Nuclear Proteins,
pubmed-meshheading:15279810-Phenotype,
pubmed-meshheading:15279810-Phosphorylation,
pubmed-meshheading:15279810-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15279810-Radiation, Ionizing,
pubmed-meshheading:15279810-S Phase,
pubmed-meshheading:15279810-Syndrome,
pubmed-meshheading:15279810-Tumor Suppressor Proteins
|
| pubmed:articleTitle |
Ataxia-telangiectasia-like disorder (ATLD)-its clinical presentation and molecular basis.
|
| pubmed:affiliation |
CR-UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK. a.m.r.taylor@bham.ac.uk
|
| pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
|