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An essential role for dNTP homeostasis following CDK-induced replication stress

Abstract:

Replication stress is a common feature of cancer cells, and thus a potentially important therapeutic target. Here we show that CDK-induced replication stress is synthetic lethal with mutations disrupting dNTP homeostasis in fission yeast. Wee1 inactivation leads to increased dNTP demand and replication stress through CDK-induced firing of dormant replication origins. Subsequent dNTP depletion leads to inefficient DNA replication, DNA damage, and to genome instability. Cells respond to this re...

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

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Publisher copy:
10.1242/jcs.226969

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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Oncology
ORCID:
0000-0002-0368-7843
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ORCID:
0000-0001-9556-9221
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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Oncology
Keszthelyi, A More by this author
More by this author
Institution:
University of Oxford
Division:
MPLS Division
Department:
Zoology
Oxford college:
Keble College
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Publisher:
The Company of Biologists Ltd Publisher's website
Journal:
Journal of Cell Science Journal website
Volume:
132
Pages:
Article: jcs226969
Publication date:
2019-01-23
Acceptance date:
2019-01-02
DOI:
EISSN:
1477-9137
ISSN:
0021-9533
Pubs id:
pubs:965978
URN:
uri:1d7197ce-bdc6-44bd-bac6-d6efc9bd1c86
UUID:
uuid:1d7197ce-bdc6-44bd-bac6-d6efc9bd1c86
Local pid:
pubs:965978

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