Phosphorylation of Slx4 by Mec1 and Tel1 regulates the single-strand annealing mode of DNA repair in budding yeast
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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.
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Checkpoints actively stimulate repair processes and, in higher eukaryotes, trigger apoptosis when damage cannot be successfully dealt with.
“The checkpoints also actively stimulate the repair processes [1–9] and, in higher eukaryotes, trigger the apoptotic response, if damage cannot be dealt with successfully [10–12].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [5]
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- Authors
- Flott, S., Alabert, C., Toh, G. W., Toth, R., Sugawara, N., Campbell, D. G., Haber, J. E., Pasero, P., & Rouse, J.
- Affiliations
- University of Dundee (GB)
- Centre National de la Recherche Scientifique (FR)
- Rosenstiel Basic Medical Sciences Research Centre, Waltham, Massachusetts
- Corresponding author
- Rouse, John
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2007-09-01
- Volume
- 27
- Issue
- 18
- Pages
- 6433-6445
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC2099619
- OpenAlex
- W2123829918
- Cited by
- 107
- References
- 59
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 10 · 2013: 8 · 2012: 7
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- HAL (submittedVersion)
- Funders
- Medical Research Council
- National Institute of General Medical Sciences (R01GM020056, R01GM061766)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- SLX4, Mec1 kinase, protein phosphorylation, single-strand annealing, DNA repair, Sgs1 helicase, RAD1, translesion synthesis, DNA damage tolerance, Saccharomyces cerevisiae
- MeSH terms
- DNA Repair, DNA, Fungal, Endodeoxyribonucleases, Fungal Proteins, Methyl Methanesulfonate, Models, Biological, Phosphorylation, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins
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