AI Article Synopsis
- DNA repair pathways help cancer cells survive damage from therapies, and tyrosine kinase receptors (TKRs) are involved in regulating these pathways.
- TIE2, a TKR found in high levels in gliomas, moves to the nucleus after ionizing radiation and enhances a specific DNA repair mechanism, leading to resistance against radiation.
- TIE2 phosphorylates histone H4 at tyrosine 51, creating a signal for the proto-oncogene ABL1, highlighting its role in connecting genotoxic stress to the DNA repair process.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065225 | PMC |
| http://dx.doi.org/10.1126/sciadv.1501290 | DOI Listing |
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