Histone H3K36 trimethylation (H3K36me3) is frequently lost in multiple cancer types, identifying it as an important therapeutic target. Here we identify a synthetic lethal interaction in which H3K36me3-deficient cancers are acutely sensitive to WEE1 inhibition. We show that RRM2, a ribonucleotide reductase subunit, is the target of this synthetic lethal interaction. RRM2 is regulated by two pathways here: first, H3K36me3 facilitates RRM2 expression through transcription initiation factor recr...Expand abstract
- Publication status:
- Peer review status:
- Peer reviewed
- Publisher's version
- Copyright holder:
- Pfister et al.
- Copyright date:
- Copyright © 2015 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Open Access funded by Medical Research Council.
Inhibiting WEE1 selectively kills histone H3K36me3-deficient cancers by dNTP starvation
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