Vaccinia-related kinase 1 (VRK1) is an upstream nucleosomal kinase required for the assembly of 53BP1 foci in response to ionizing radiation-induced DNA damage

Marta Sanz-Garciá, Diana M. Monsalve, Ana Sevilla, Pedro A. Lazo

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

30 Citas (Scopus)

Resumen

Cellular responses to DNA damage require the formation of protein complexes in a highly organized fashion. The complete molecular components that participate in the sequential signaling response to DNA damage remain unknown. Here we demonstrate that vaccinia-related kinase 1 (VRK1) in resting cells plays an important role in the formation of ionizing radiationinduced foci that assemble on the 53BP1 scaffold protein during the DNA damage response. The kinase VRK1 is activated by DNA double strand breaks induced by ionizing radiation (IR) and specifically phosphorylates 53BP1 in serum-starved cells. VRK1 knockdown resulted in the defective formation of 53BP1 foci in response to IR both in number and size. This observed effect on 53BP1 foci is p53- and ataxia-telangiectasia mutated (ATM)-independent and can be rescued with VRK1 mutants resistant to siRNA. VRK1 knockdown also prevented the activating phosphorylation of ATM, CHK2, and DNA-dependent protein kinase in response to IR. VRK1 activation in response to DNA damage is a novel and early step in the signaling of mammalian DNA damage responses.

Idioma originalInglés estadounidense
Páginas (desde-hasta)23757-23768
Número de páginas12
PublicaciónJournal of Biological Chemistry
Volumen287
N.º28
DOI
EstadoPublicada - jul 6 2012
Publicado de forma externa

All Science Journal Classification (ASJC) codes

  • Bioquímica
  • Biología molecular
  • Biología celular

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