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PredicateObject
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
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
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