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Genes Dev.-2010-Nestoras-1145-59.pdf (2.14 MB)

Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms

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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 Liu
The 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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Genes & Development

ISSN

0890-9369

Publisher

Cold Spring Harbor Laboratory Press

Issue

11

Volume

24

Page range

1145-1159

Department affiliated with

  • Chemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

First Open Access (FOA) Date

2017-11-08

First Compliant Deposit (FCD) Date

2017-11-08

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