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Heterochromatin-Dependent Replication Stress: A Lesson from IDH1/2 Mutants.

Cancer research - 15 Sept 2023

Zou Lee

Abstract excerpt

Oncogenic point mutants of isocitrate dehydrogenases 1 and 2 (IDH2) generate 2-hydroxyglutarate, which inhibits lysine demethylases and increases heterochromatin. Tumor cells expressing IDH mutants are sensitive to PARP inhibitors (PARPi), offering an opportunity to eliminate IDH-driven tumor cells in therapy. Expression of an oncogenic IDH1 mutant in cells leads to aberrant heterochromatin formation at DNA...

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PMID: 37433029
DOI: 10.1158/0008-5472.CAN-23-2015

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