Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Genetic analysis of the DNA-dependent protein kinase reveals an inhibitoryrole of Ku in late S-G(2) phase DNA double-strand break repair
Autore:
Fukushima, T; Takata, M; Morrison, C; Araki, R; Fujimori, A; Abe, M; Tatsumi, K; Jasin, M; Dhar, PK; Sonoda, E; Chiba, T; Takeda, S;
Indirizzi:
Kyoto Univ, Fac Med, CREST Res Project, Sakyo Ku, Kyoto 6068501, Japan Kyoto Univ Kyoto Japan 6068501 s Project, Sakyo Ku, Kyoto 6068501, Japan Univ Edinburgh, Inst Cell & Mol Biol, Edinburgh EH9 3JR, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland EH9 3JR Midlothian, Scotland Natl Inst Radiol Sci, Inage Ku, Chiba 2638555, Japan Natl Inst Radiol SciChiba Japan 2638555 Inage Ku, Chiba 2638555, Japan Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA Mem Sloan Kettering Canc Ctr New York NY USA 10021 New York, NY 10021 USA Cornell Univ, Grad Sch Med Sci, New York, NY 10021 USA Cornell Univ New York NY USA 10021 ad Sch Med Sci, New York, NY 10021 USA Kyoto Univ, Grad Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Sakyo Ku, Kyoto 6068507, Japan Kyoto Univ Kyoto Japan 6068507 & Hepatol,Sakyo Ku, Kyoto 6068507, Japan
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 48, volume: 276, anno: 2001,
pagine: 44413 - 44418
SICI:
0021-9258(20011130)276:48<44413:GAOTDP>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
SEVERE COMBINED IMMUNODEFICIENCY; CELL ANTIGEN RECEPTOR; V(D)J RECOMBINATION; LIGASE-IV; HOMOLOGOUS RECOMBINATION; IONIZING-RADIATION; CATALYTIC SUBUNIT; VERTEBRATE CELLS; MAMMALIAN-CELLS; IN-VIVO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Takeda, S Kyoto Univ, Fac Med, CREST Res Project, Sakyo Ku, Konoe Yoshida,Kyoto 6068501, Japan Kyoto Univ Konoe Yoshida Kyoto Japan 6068501 oto 6068501, Japan
Citazione:
T. Fukushima et al., "Genetic analysis of the DNA-dependent protein kinase reveals an inhibitoryrole of Ku in late S-G(2) phase DNA double-strand break repair", J BIOL CHEM, 276(48), 2001, pp. 44413-44418

Abstract

Two major complementary double-strand break (DSB) repair pathways exist invertebrates, homologous recombination (HR), which involves Rad54, and non-homologous end joining, which requires the DNA-dependent protein kinase (DNA-PK). DNA-PK comprises a catalytic subunit (DNA-PKcs) and a DNA-binding Ku70 and Ku80 heterodimer. To define the activities of individual DNA-PK components in DSB repair, we targeted the DNA-PKcs gene in chicken DT40 cells. DNA-PKcs deficiency caused a DSB repair defect that was, unexpectedly, suppressed by KU70 disruption. We have shown previously that genetic ablation of Ku70 confers RAD54-dependent radioresistance on S-G(2) phase cells, when sister chromatids are available for HR repair. To test whether direct interference by Ku70 with HR might explain the Ku70(-/-)/DNA-PKcs(-/-/-) radioresistance, we monitored HR activities directly in Ku- and DNA-PKcs-deficientcells. The frequency of intrachromosomal HR induced by the I-SceI restriction enzyme was increased in the absence of Ku but not of DNA-PKcs. Significantly, abrogation of HR activity by targeting RAD54 in Ku 70(-/-) or DNA-PKcs(-/-/-) cells caused extreme radiosensitivity, suggesting that the relative radioresistance seen with loss of Ku70 was because of HR-dependent repair pathways. Our findings suggest that Ku can interfere with HR-mediated DSBrepair, perhaps competing with HR for DSB recognition.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 07:32:56