Your browser doesn't support javascript.
loading
Disruption of Runx1 and Runx3 leads to bone marrow failure and leukemia predisposition due to transcriptional and DNA repair defects.
Wang, Chelsia Qiuxia; Krishnan, Vaidehi; Tay, Lavina Sierra; Chin, Desmond Wai Loon; Koh, Cai Ping; Chooi, Jing Yuan; Nah, Giselle Sek Suan; Du, Linsen; Jacob, Bindya; Yamashita, Namiko; Lai, Soak Kuan; Tan, Tuan Zea; Mori, Seiichi; Tanuichi, Ichiro; Tergaonkar, Vinay; Ito, Yoshiaki; Osato, Motomi.
Afiliación
  • Wang CQ; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673, Singapore.
  • Krishnan V; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • Tay LS; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • Chin DW; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • Koh CP; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • Chooi JY; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • Nah GS; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673, Singapore.
  • Du L; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • Jacob B; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • Yamashita N; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • Lai SK; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • Tan TZ; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • Mori S; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • Tanuichi I; Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
  • Tergaonkar V; Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673, Singapore. Electronic address: vinayt@imcb.a-star.edu.sg.
  • Ito Y; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673, Singapore. Electronic address: csiitoy@nus.edu.sg.
  • Osato M; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673, Singapore; Institute of Bioengineering and Nanotechnology, A(∗)STAR, Singapore 138669, Singapore. Electronic address:
Cell Rep ; 8(3): 767-82, 2014 Aug 07.
Article en En | MEDLINE | ID: mdl-25066130
The RUNX genes encode transcription factors involved in development and human disease. RUNX1 and RUNX3 are frequently associated with leukemias, yet the basis for their involvement in leukemogenesis is not fully understood. Here, we show that Runx1;Runx3 double-knockout (DKO) mice exhibited lethal phenotypes due to bone marrow failure and myeloproliferative disorder. These contradictory clinical manifestations are reminiscent of human inherited bone marrow failure syndromes such as Fanconi anemia (FA), caused by defective DNA repair. Indeed, Runx1;Runx3 DKO cells showed mitomycin C hypersensitivity, due to impairment of monoubiquitinated-FANCD2 recruitment to DNA damage foci, although FANCD2 monoubiquitination in the FA pathway was unaffected. RUNX1 and RUNX3 interact with FANCD2 independently of CBFß, suggesting a nontranscriptional role for RUNX in DNA repair. These findings suggest that RUNX dysfunction causes DNA repair defect, besides transcriptional misregulation, and promotes the development of leukemias and other cancers.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Médula Ósea / Leucemia / Reparación del ADN / Subunidad alfa 2 del Factor de Unión al Sitio Principal / Subunidad alfa 3 del Factor de Unión al Sitio Principal / Anemia de Fanconi Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2014 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Médula Ósea / Leucemia / Reparación del ADN / Subunidad alfa 2 del Factor de Unión al Sitio Principal / Subunidad alfa 3 del Factor de Unión al Sitio Principal / Anemia de Fanconi Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2014 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos