Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms
| Autor: | Asma Hadi Mohammed, Ann-Sofie Schreurs, Marius Poitelea, Konstantinos Nestoras, Birthe B. Kragelund, Olaf Nielsen, Christian Holmberg, Mark A. Osborne, Antony M. Carr, Cong Liu, Charlotte O'Shea, Charly Chahwan, Adam T. Watson, Oliver Fleck |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
DNA damage
Protein subunit Saccharomyces cerevisiae Active Transport Cell Nucleus Cell Cycle Proteins 03 medical and health sciences Gene Expression Regulation Fungal Ribonucleotide Reductases Schizosaccharomyces Genetics Transcriptional regulation 030304 developmental biology Regulation of gene expression 0303 health sciences Alanine biology 030302 biochemistry & molecular biology Subcellular localization biology.organism_classification Protein Subunits Ribonucleotide reductase Biochemistry Mutagenesis Schizosaccharomyces pombe Proteins Nuclear transport Developmental Biology Research Paper |
| ISSN: | 0890-9369 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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