Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage
| Autor: | John Rouse, Sonja Flott |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Alkylation DNA Repair DNA repair DNA damage RecQ helicase Cell Cycle Proteins Saccharomyces cerevisiae Protein Serine-Threonine Kinases Biology Biochemistry Fungal Proteins chemistry.chemical_compound Gene Expression Regulation Fungal Phosphorylation DNA Fungal Molecular Biology Endodeoxyribonucleases Intracellular Signaling Peptides and Proteins Helicase Cell Biology Cell cycle Checkpoint Kinase 2 DNA Alkylation chemistry Checkpoint Kinase 1 biology.protein Protein Kinases Cell Division Gene Deletion DNA Research Article DNA Damage Mutagens Signal Transduction Sgs1 |
| Zdroj: | Biochemical Journal. 391:325-333 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20050768 |
| Popis: | Members of the RecQ family of DNA helicases, mutated in several syndromes associated with cancer predisposition, are key regulators of genome stability. The Saccharomyces cerevisiae SLX4 gene is required for cell viability in the absence of Sgs1, the only yeast RecQ helicase. SLX4 encodes one subunit of the heterodimeric Slx1–Slx4 endonuclease, although its cellular function is not clear. Slx1–Slx4 was reported to preferentially cleave replication fork-like structures in vitro, and cells lacking SLX4 are hypersensitive to DNA alkylation damage. Here we report that Slx4 becomes phosphorylated in cells exposed to a wide range of genotoxins. Even though it has been proposed that the role of Slx4 is restricted to S-phase, Slx4 phosphorylation is observed in cells arrested in G1 or G2 phases of the cell cycle, but not during an unperturbed cell cycle. Slx4 phosphorylation is completely abolished in cells lacking the Mec1 and Tel1 protein kinases, critical regulators of genome stability, but is barely affected in the absence of both Rad53 and Chk1 kinases. Finally we show that, whereas both Slx1 and Slx4 are dispensable for activation of cell-cycle checkpoints, Slx4, but not Slx1, is required for repair of DNA alkylation damage in both aynchronously growing cells and in G2-phase-arrested cells. These results reveal Slx4 as a new target of the Mec1/Tel1 kinases, with a crucial role in DNA repair that is not restricted to the processing of stalled replisomes. |
| Databáze: | OpenAIRE |
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