Phosphorylation of Slx4 by Mec1 and Tel1 regulates the single-strand annealing mode of DNA repair in budding yeast
| Autor: | Sonja Flott, James E. Haber, Geraldine W. Toh, John Rouse, Neal Sugawara, David G. Campbell, Philippe Pasero, Rachel Toth, Constance Alabert |
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| Přispěvatelé: | Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Saccharomyces cerevisiae Proteins
DNA Repair DNA polymerase DNA damage DNA repair Saccharomyces cerevisiae Protein Serine-Threonine Kinases Models Biological Fungal Proteins 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Phosphorylation DNA Fungal Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences Endodeoxyribonucleases biology DNA synthesis Intracellular Signaling Peptides and Proteins [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Articles Cell Biology Methyl Methanesulfonate Proliferating cell nuclear antigen chemistry Biochemistry biology.protein Replisome 030217 neurology & neurosurgery DNA Sgs1 |
| Zdroj: | Molecular and Cellular Biology Molecular and Cellular Biology, American Society for Microbiology, 2007, 27 (18), pp.6433-6445. ⟨10.1128/MCB.00135-07⟩ |
| ISSN: | 0270-7306 1098-5549 |
| DOI: | 10.1128/MCB.00135-07⟩ |
| Popis: | Budding yeast (Saccharomyces cerevisiae) Slx4 is essential for cell viability in the absence of the Sgs1 helicase and for recovery from DNA damage. Here we report that cells lacking Slx4 have difficulties in completing DNA synthesis during recovery from replisome stalling induced by the DNA alkylating agent methyl methanesulfonate (MMS). Although DNA synthesis restarts during recovery, cells are left with unreplicated gaps in the genome despite an increase in translesion synthesis. In this light, epistasis experiments show that SLX4 interacts with genes involved in error-free bypass of DNA lesions. Slx4 associates physically, in a mutually exclusive manner, with two structure-specific endonucleases, Rad1 and Slx1, but neither of these enzymes is required for Slx4 to promote resistance to MMS. However, Rad1-dependent DNA repair by single-strand annealing (SSA) requires Slx4. Strikingly, phosphorylation of Slx4 by the Mec1 and Tel1 kinases appears to be essential for SSA but not for cell viability in the absence of Sgs1 or for cellular resistance to MMS. These results indicate that Slx4 has multiple functions in responding to DNA damage and that a subset of these are regulated by Mec1/Tel1-dependent phosphorylation. |
| Databáze: | OpenAIRE |
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