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Article Dans Une Revue Biochemical Journal Année : 2008

Identification and characterisation of FUS/TLS as a new target of ATM

Mary Gardiner
  • Fonction : Auteur
Rachel Toth
  • Fonction : Auteur
Franck Vandermoere
Nicholas A Morrice
  • Fonction : Auteur

Résumé

ATM, ATR and DNA–PK, important regulators of genome stability, belong to the PI(3)-kinase-like kinase (PIKK) family of protein kinases. In this study, DNA affinity chromatography was used to identify DNA binding proteins phosphorylated by these kinases. This resulted in the identification of FUS/TLS as an in vitro target of the PIKK kinases. FUS is a member of the Ewing's sarcoma family of proteins, and that appear to play a role in regulating genome stability since mice lacking FUS show chromosomal instability and defects in meiosis. The residues in FUS that are phosphorylated in vitro and in vivo were identified and phospho-specific antibodies were generated to demonstrate that FUS becomes phosphorylated at Ser42 in vivo primarily in response to agents that cause double-strand breaks (DSBs). DSB-induced FUS phosphorylation in vivo at Ser42 requires ATM and not DNA–PK. Although Ser42 is retained in the oncogenic FUS-CHOP fusion caused by a t(12;16)(q13;p11) chromosomal translocation, Ser42 in FUS-CHOP is not phosphorylated after DNA damage. These results identify FUS as a new target of the ATM signalling pathway and strengthen the notion that FUS regulates genome stability.

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Dates et versions

hal-00479035 , version 1 (30-04-2010)

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Mary Gardiner, Rachel Toth, Franck Vandermoere, Nicholas A Morrice, John Rouse. Identification and characterisation of FUS/TLS as a new target of ATM. Biochemical Journal, 2008, 415 (2), pp.297-307. ⟨10.1042/BJ20081135⟩. ⟨hal-00479035⟩

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