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Congenital bone marrow failure in DNA-PKcs mutant mice associated with deficiencies in DNA repair
https://repo.qst.go.jp/records/46215
https://repo.qst.go.jp/records/462152160aee9-39ad-4c45-94da-39a0f609f1fd
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-11-22 | |||||
| タイトル | ||||||
| タイトル | Congenital bone marrow failure in DNA-PKcs mutant mice associated with deficiencies in DNA repair | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Zhang, Shichuan
× Zhang, Shichuan× Yajima, Hirohiko× et.al× 矢島 浩彦 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The nonhomologous end-joining (NHEJ) pathway is essential for radioresistance and lymphocyte- specific V(D)J (variable [diversity] joining) recombi- nation. Defects in NHEJ also impair hematopoietic stem cell (HSC) activity with age but do not affect the initial establishment of HSC reserves. In this paper, we report that, in contrast to deoxyribonucleic acid (DNA)–dependent protein kinase catalytic subunit (DNA-PKcs)–null mice, knockin mice with the DNA-PKcs3A/3A allele, which codes for three alanine substitutions at the mouse Thr2605 phos- phorylation cluster, die prematurely because of congenital bone marrow failure. Impaired proliferation of DNA- PKcs3A/3A HSCs is caused by excessive DNA damage and p53-dependent apoptosis. In addition, increased apopto- sis in the intestinal crypt and epidermal hyperpigmenta- tion indicate the presence of elevated genotoxic stress and p53 activation. Analysis of embryonic fibroblasts further reveals that DNA-PKcs3A/3A cells are hypersensitive to DNA cross-linking agents and are defective in both homologous recombination and the Fanconi anemia DNA damage response pathways. We conclude that phosphory- lation of DNA-PKcs is essential for the normal activation of multiple DNA repair pathways, which in turn is critical for the maintenance of diverse populations of tissue stem cells in mice. | |||||
| 書誌情報 |
Journal of Cell Biology 巻 193, 号 2, p. 295-305, 発行日 2011-04 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0021-9525 | |||||
