Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms.
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.
Nestoras
Konstantinos
K
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN19RQ, United Kingdom.
Mohammed
Asma Hadi
AH
Schreurs
Ann-Sofie
AS
Fleck
Oliver
O
Watson
Adam T
AT
Poitelea
Marius
M
O'Shea
Charlotte
C
Chahwan
Charly
C
Holmberg
Christian
C
Kragelund
Birthe B
BB
Nielsen
Olaf
O
Osborne
Mark
M
Carr
Antony M
AM
Liu
Cong
C
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000409:Alanine / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D016296:Mutagenesis; D021122:Protein Subunits / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D021122:Protein Subunits; D029702:Schizosaccharomyces pombe Proteins; C102445:Spd1 protein, S pombe; C080926:cdc22 protein, S pombe; D012264:Ribonucleotide Reductases; C080927:SUC22 protein, S pombe; D000409:Alanine