Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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.
OriginalsprogEngelsk
TidsskriftGenes & Development
Vol/bind24
Udgave nummer11
Sider (fra-til)1145-1159
Antal sider15
ISSN0890-9369
DOI
StatusUdgivet - 1 jun. 2010

ID: 33576513