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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2006-7-26
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pubmed:abstractText |
Ionizing radiation (IR) induces a variety of DNA lesions. The most significant lesion is a DNA double-strand break (DSB), which is repaired by homologous recombination or nonhomologous end joining (NHEJ) pathway. Since we previously demonstrated that IR-responsive protein 53BP1 specifically enhances activity of DNA ligase IV, a DNA ligase required for NHEJ, we investigated responses of 53BP1-deficient chicken DT40 cells to IR. 53BP1-deficient cells showed increased sensitivity to X-rays during G1 phase. Although intra-S and G2/M checkpoints were intact, the frequency of isochromatid-type chromosomal aberrations was elevated after irradiation in 53BP1-deficient cells. Furthermore, the disappearance of X-ray-induced gamma-H2AX foci, a marker of DNA DSBs, was prolonged in 53BP1-deficient cells. Thus, the elevated X-ray sensitivity in G1 phase cells was attributable to repair defect for IR-induced DNA-damage. Epistasis analysis revealed that 53BP1 plays a role in a pathway distinct from the Ku-dependent and Artemis-dependent NHEJ pathways, but requires DNA ligase IV. Strikingly, disruption of the 53BP1 gene together with inhibition of phosphatidylinositol 3-kinase family by wortmannin completely abolished colony formation by cells irradiated during G1 phase. These results demonstrate that the 53BP1-dependent repair pathway is important for survival of cells irradiated with IR during the G1 phase of the cell cycle.
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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/Androstadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/DCLRE1C protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA ligase (ATP),
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/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Ku autoantigen,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/TP53BP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1356-9597
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pubmed:author |
pubmed-author:AdachiNoritakaN,
pubmed-author:DateTakayasuT,
pubmed-author:HashimotoMitsumasaM,
pubmed-author:IshiaiMasamichiM,
pubmed-author:IwabuchiKuniyoshiK,
pubmed-author:KoyamaHidekiH,
pubmed-author:KuriharaTakayukiT,
pubmed-author:MatsuiTadashiT,
pubmed-author:ShimizuHirokoH,
pubmed-author:TakataMinoruM,
pubmed-author:TauchiHiroshiH,
pubmed-author:YamamotoKen-ichiK
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pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
935-48
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16866876-Androstadienes,
pubmed-meshheading:16866876-Animals,
pubmed-meshheading:16866876-Antigens, Nuclear,
pubmed-meshheading:16866876-Cell Cycle,
pubmed-meshheading:16866876-Cell Division,
pubmed-meshheading:16866876-Cell Survival,
pubmed-meshheading:16866876-Chickens,
pubmed-meshheading:16866876-Chromosome Aberrations,
pubmed-meshheading:16866876-DNA Ligases,
pubmed-meshheading:16866876-DNA Repair,
pubmed-meshheading:16866876-DNA-Binding Proteins,
pubmed-meshheading:16866876-Dose-Response Relationship, Radiation,
pubmed-meshheading:16866876-Drug Resistance,
pubmed-meshheading:16866876-G1 Phase,
pubmed-meshheading:16866876-G2 Phase,
pubmed-meshheading:16866876-Genes, cdc,
pubmed-meshheading:16866876-Histones,
pubmed-meshheading:16866876-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16866876-Models, Biological,
pubmed-meshheading:16866876-Nuclear Proteins,
pubmed-meshheading:16866876-Phosphoproteins,
pubmed-meshheading:16866876-Radiation Tolerance,
pubmed-meshheading:16866876-Recombination, Genetic,
pubmed-meshheading:16866876-S Phase,
pubmed-meshheading:16866876-Sequence Homology, Nucleic Acid,
pubmed-meshheading:16866876-Signal Transduction,
pubmed-meshheading:16866876-X-Rays
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pubmed:year |
2006
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pubmed:articleTitle |
53BP1 contributes to survival of cells irradiated with X-ray during G1 without Ku70 or Artemis.
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pubmed:affiliation |
Department of Biochemistry, Kanazawa Medical University, Daigaku 1-1, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan. kuni-kmu@kanazawa-med.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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