Supplementary Materials

Supplementary Material for:

2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity

Parker L. Sulkowski, Christopher D. Corso, Nathaniel D. Robinson, Susan E. Scanlon, Karin R. Purshouse, Hanwen Bai, Yanfeng Liu, Ranjini K. Sundaram, Denise C. Hegan, Nathan R. Fons, Gregory A. Breuer, Yuanbin Song, Ketu Mishra-Gorur, Henk M. De Feyter, Robin A. de Graaf, Yulia V. Surovtseva, Maureen Kachman, Stephanie Halene, Murat Günel, Peter M. Glazer,* Ranjit S. Bindra*

*Corresponding author. Email: ranjit.bindra{at}yale.edu (R.S.B.); peter.glazer{at}yale.edu (P.M.G.)

Published 1 February 2017, Sci. Transl. Med. 9, eaal2463 (2017)
DOI: 10.1126/scitranslmed.aal2463

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Establishment and characterization of IDH mutant and WT cell models.
  • Fig. S2. Characterization of the DNA DSB repair defect in IDH mutant cells.
  • Fig. S3. Cell growth and viability assays in response to DNA repair and DNA damage response inhibitors.
  • Fig. S4. Increased sensitivity of IDH mutant cells to PARP inhibitors alone and in combination with cisplatin.
  • Fig. S5. Additional characterization of the impact of 2HG on DNA DSB repair.
  • Fig. S6. Manipulation of IDH and L2HGDH by siRNAs and impact on DNA DSB repair.
  • Fig. S7. Rescue of 2HG-induced HR defect by αKG, role of KDM4A/B in DNA repair regulation by mutant IDH1, and lack of correlation with NAD+ concentration.
  • Fig. S8. Additional glioma cell and xenograft data.
  • Table S1. STR profile of IDH WT parental HeLa cells.
  • Table S2. STR profile of IDH1 R132H/+ HeLa cell subclone.
  • Table S3. List of siRNAs targeting αKG-dependent dioxygenases and selected DNA repair proteins.
  • Table S4. Surviving fraction of 50% values for clonogenic survival assays.
  • References (6471)

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