Research ArticleCELL BIOLOGY

TIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1

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Science Advances  01 Apr 2016:
Vol. 2, no. 4, e1501290
DOI: 10.1126/sciadv.1501290

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DNA repair pathways enable cancer cells to survive DNA damage induced after genotoxic therapies. Tyrosine kinase receptors (TKRs) have been reported as regulators of the DNA repair machinery. TIE2 is a TKR overexpressed in human gliomas at levels that correlate with the degree of increasing malignancy. Following ionizing radiation, TIE2 translocates to the nucleus, conferring cells with an enhanced nonhomologous end-joining mechanism of DNA repair that results in a radioresistant phenotype. Nuclear TIE2 binds to key components of DNA repair and phosphorylates H4 at tyrosine 51, which, in turn, is recognized by the proto-oncogene ABL1, indicating a role for nuclear TIE2 as a sensor for genotoxic stress by action as a histone modifier. H4Y51 constitutes the first tyrosine phosphorylation of core histones recognized by ABL1, defining this histone modification as a direct signal to couple genotoxic stress with the DNA repair machinery.

  • Cell biology
  • DNA repair
  • oncogenes
  • TIE2
  • ABL1
  • ANG1
  • NHEJ

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