ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma

  title={ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma},
  author={Carl Koschmann and Anda-Alexandra Calinescu and Felipe J. Nunez and Alan Mackay and Janet Fazal-Salom and Daniel Thomas and Flor M M{\'e}ndez and Neha Kamran and Marta B Dzaman and Lakshman Mulpuri and Johnathon Krasinkiewicz and Robert Doherty and Rosemary M Lemons and Jacqueline A Brosnan-Cashman and Youping Li and Soyeon Roh and Lili Zhao and Henry D. Appelman and David Ferguson and Vera Gorbunova and Alan K Meeker and Chris Jones and Pedro Ricardo Lowenstein and Maria Graciela Castro},
  journal={Science Translational Medicine},
Recent work in human glioblastoma (GBM) has documented recurrent mutations in the histone chaperone protein ATRX. We developed an animal model of ATRX-deficient GBM and showed that loss of ATRX reduces median survival and increases genetic instability. Further, analysis of genome-wide data for human gliomas showed that ATRX mutation is associated with increased mutation rate at the single-nucleotide variant (SNV) level. In mouse tumors, ATRX deficiency impairs nonhomologous end joining and… CONTINUE READING
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