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Ribonucleotide reductase requires subunit switching in hypoxia to maintain DNA replication

Abstract:

Cells exposed to hypoxia, experience replication stress but do not accumulate DNA damage, suggesting sustained DNA replication. Ribonucleotide Reductase (RNR) is the only enzyme capable of de novo synthesis of dNTPs. However, oxygen is an essential cofactor for mammalian RNR (RRM1/RRM2 and RRM1/RRM2B), leading us to question the source of dNTPs in hypoxia. Here, we show that the RRM1/RRM2B enzyme is capable of retaining activity in hypoxia and therefore is favored over RRM1/RRM2 in order to p...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.molcel.2017.03.005

Authors


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Institution:
University of Oxford
Division:
MSD
Department:
Oncology
Role:
Author
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Institution:
University of Oxford
Division:
MSD
Department:
Oncology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Oncology
Role:
Author
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Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Role:
Author
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Contributors

Institution:
University of Oxford
Division:
Societies, Other & Subsidiary Companies
Department:
Gray Cancer Institute
Role:
Contributor
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Funding agency for:
Jorgensen, C
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Funding agency for:
Foskolou, I
Grant:
C38302/A12981
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Funding agency for:
Hammond, E
Publisher:
Elsevier Publisher's website
Journal:
Molecular Cell Journal website
Volume:
66
Issue:
2
Pages:
206-220
Publication date:
2017-04-13
Acceptance date:
2017-03-02
DOI:
EISSN:
1097-4164
ISSN:
1097-2765
Source identifiers:
686272
Keywords:
Pubs id:
pubs:686272
UUID:
uuid:c87ef1cc-84d5-447d-8eb0-9068fc9040ab
Local pid:
pubs:686272
Deposit date:
2017-03-17

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