Genes Dev.-2010-Nestoras-1145-59.pdf (2.14 MB)
Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms
journal contribution
posted on 2023-06-07, 23:18 authored by Konstantinos Nestoras, Asma Hadi Mohammed, Ann-Sofie Schreurs, Oliver Fleck, Adam WatsonAdam Watson, Marius Poitelea, Charlotte O'Shea, Charly Chacwan, Christian Holmberg, Birthe B Kragelund, Olaf Nielsen, Mark Osborne, Antony CarrAntony Carr, Cong LiuCong LiuThe correct levels of deoxyribonucleotide triphosphates and their relative abundance are important to maintain genomic integrity. Ribonucleotide reductase (RNR) regulation is complex and multifaceted. RNR is regulated allosterically by two nucleotide-binding sites, by transcriptional control, and by small inhibitory proteins that associate with the R1 catalytic subunit. In addition, the subcellular localization of the R2 subunit is regulated through the cell cycle and in response to DNA damage. We show that the fission yeast small RNR inhibitor Spd1 is intrinsically disordered and regulates R2 nuclear import, as predicted by its relationship to Saccharomyces cerevisiae Dif1. We demonstrate that Spd1 can interact with both R1 and R2, and show that the major restraint of RNR in vivo by Spd1 is unrelated to R2 subcellular localization. Finally, we identify a new behavior for RNR complexes that potentially provides yet another mechanism to regulate dNTP synthesis via modulation of RNR complex architecture.
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Publication status
- Published
File Version
- Published version
Journal
Genes & DevelopmentISSN
0890-9369Publisher
Cold Spring Harbor Laboratory PressExternal DOI
Issue
11Volume
24Page range
1145-1159Department affiliated with
- Chemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06First Open Access (FOA) Date
2017-11-08First Compliant Deposit (FCD) Date
2017-11-08Usage metrics
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