rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
22
|
pubmed:dateCreated |
1998-1-5
|
pubmed:abstractText |
Heterodimers of the 70 and 80 kDa Ku autoantigens (Ku70 and Ku80) activate the DNA-dependent protein kinase (DNA-PK). Mutations in any of the three subunits of this protein kinase (Ku70, Ku80 and DNA-PKcs) lead to sensitivity to ionizing radiation (IR) and to DNA double-strand breaks, and V(D)J recombination product formation defects. Here we show that the IR repair, DNA end binding and DNA-PK defects in Ku70-/- embryonic stem cells can be counteracted by introducing epitope-tagged wild-type Ku70 cDNA. Truncations and chimeras of Ku70 were used to identify the regions necessary for DNA end binding and IR repair. Site-specific mutational analysis revealed a core region of Ku70 responsible for DNA end binding and heterodimerization. The propensity for Ku70 to associate with Ku80 and to bind DNA correlates with the ability to activate DNA-PK, although two mutants showed that the roles of Ku70 in DNA-PK activation and IR repair are separate. Mutation of DNA-PK autophosphorylation sites and other structural motifs in Ku70 showed that these sites are not necessary for IR repair in vivo. These studies reveal Ku70 features required for double-strand break repair.
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-1375268,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-1406679,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-1486241,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-1632793,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-1730599,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-2247067,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-2466842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-7276162,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-7516471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-7565721,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-7671312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-7816841,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-7846073,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-7855602,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-7889575,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-7939667,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-7957065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8031790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8041718,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8073286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8206892,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8332451,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8352745,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8509423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8604297,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8621537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8637578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8657125,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8700231,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8743882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8754818,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8756676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8756720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8799130,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-8972848,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-9024627,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-9109492,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-9223317,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-9312071,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9362500-9338103
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Activated Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ku autoantigen,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PRKDC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/XRCC5 protein, human
|
pubmed:status |
MEDLINE
|
pubmed:month |
Nov
|
pubmed:issn |
0261-4189
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
17
|
pubmed:volume |
16
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
6874-85
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:9362500-Amino Acid Sequence,
pubmed-meshheading:9362500-Antigens, Nuclear,
pubmed-meshheading:9362500-Cell Line,
pubmed-meshheading:9362500-Consensus Sequence,
pubmed-meshheading:9362500-DNA Damage,
pubmed-meshheading:9362500-DNA Helicases,
pubmed-meshheading:9362500-DNA Repair,
pubmed-meshheading:9362500-DNA-Activated Protein Kinase,
pubmed-meshheading:9362500-DNA-Binding Proteins,
pubmed-meshheading:9362500-Dimerization,
pubmed-meshheading:9362500-Dose-Response Relationship, Radiation,
pubmed-meshheading:9362500-Genetic Complementation Test,
pubmed-meshheading:9362500-Humans,
pubmed-meshheading:9362500-Molecular Sequence Data,
pubmed-meshheading:9362500-Mutation,
pubmed-meshheading:9362500-Nuclear Proteins,
pubmed-meshheading:9362500-Protein Binding,
pubmed-meshheading:9362500-Protein-Serine-Threonine Kinases,
pubmed-meshheading:9362500-Radiation, Ionizing,
pubmed-meshheading:9362500-Radiation Tolerance,
pubmed-meshheading:9362500-Sequence Homology, Amino Acid
|
pubmed:year |
1997
|
pubmed:articleTitle |
Double-strand break repair by Ku70 requires heterodimerization with Ku80 and DNA binding functions.
|
pubmed:affiliation |
Division of Tumor Immunology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
|
pubmed:publicationType |
Journal Article
|