The ribonucleotide reductase inhibitor, Sml1, is sequentially phosphorylated, ubiquitylated and degraded in response to DNA damage
| Autor: | Rodney Rothstein, Bethany L. Andreson, Amitabha Gupta, Bilyana Georgieva |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Proteasome Endopeptidase Complex
Saccharomyces cerevisiae Proteins DNA damage Ubiquitin-Protein Ligases Deoxyribonucleotides Down-Regulation Ribonucleotide reductase inhibitor Genotoxic Stress Genome Integrity Repair and Replication medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Ubiquitin Genetics medicine Phosphorylation 030304 developmental biology 0303 health sciences Mutation biology Ubiquitination Ubiquitin ligase Ribonucleotide reductase Proteasome Biochemistry Amino Acid Substitution Ubiquitin-Conjugating Enzymes biology.protein Carrier Proteins 030217 neurology & neurosurgery DNA Damage |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Regulation of ribonucleotide reductase (RNR) is important for cell survival and genome integrity in the face of genotoxic stress. The Mec1/Rad53/Dun1 DNA damage response kinase cascade exhibits multifaceted controls over RNR activity including the regulation of the RNR inhibitor, Sml1. After DNA damage, Sml1 is degraded leading to the up-regulation of dNTP pools by RNR. Here, we probe the requirements for Sml1 degradation and identify several sites required for in vivo phosphorylation and degradation of Sml1 in response to DNA damage. Further, in a strain containing a mutation in Rnr1, rnr1-W688G, mutation of these sites in Sml1 causes lethality. Degradation of Sml1 is dependent on the 26S proteasome. We also show that degradation of phosphorylated Sml1 is dependent on the E2 ubiquitin-conjugating enzyme, Rad6, the E3 ubiquitin ligase, Ubr2, and the E2/E3-interacting protein, Mub1, which form a complex previously only implicated in the ubiquitylation of Rpn4. |
| Databáze: | OpenAIRE |
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