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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 deoxyribonucleotide triphosphates (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 f...

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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.molcel.2017.03.005

Authors


Foskolou, IP More by this author
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ORCID:
0000-0003-1894-7158
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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Oncology
ORCID:
0000-0002-3504-1553
Olcina, MM More by this author
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Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry; Inorganic Chemistry
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King’s College London GTA More from this funder
Publisher:
Elsevier Publisher's website
Journal:
Molecular Cell Journal website
Volume:
66
Issue:
2
Pages:
206-220.e9
Publication date:
2017-04-05
Acceptance date:
2017-03-07
DOI:
EISSN:
1097-4164
ISSN:
1097-2765
Pubs id:
pubs:690316
URN:
uri:f72d47f2-2000-4fa2-9c6f-8bc42067f88e
UUID:
uuid:f72d47f2-2000-4fa2-9c6f-8bc42067f88e
Local pid:
pubs:690316

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