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Inhibiting WEE1 selectively kills histone H3K36me3-deficient cancers by dNTP starvation

Abstract:

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...

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Publication status:
Published
Peer review status:
Peer reviewed
Version:
Publisher's version

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Publisher copy:
10.1016/j.ccell.2015.09.015

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Institution:
University of Oxford
Department:
Oxford, MSD, Oncology
Role:
Author
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Institution:
University of Oxford
Department:
Oxford, MSD, Oncology
Role:
Author
More by this author
Institution:
University of Oxford
Department:
Oxford, MSD, Oncology
Role:
Author
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Medical Research Council More from this funder
Publisher:
Elsevier (Cell Press) Publisher's website
Journal:
Cancer Cell Journal website
Volume:
28
Issue:
5
Pages:
557–568
Publication date:
2015-01-01
DOI:
ISSN:
1878-3686
URN:
uuid:df820d16-c445-43ef-a0f0-8e0183d370a3
Source identifiers:
573105
Local pid:
pubs:573105

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