Phosphorylation of Rad55 on Serines 2, 8, and 14 Is Required for Efficient Homologous Recombination in the Recovery of Stalled Replication Forks
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DNA damage checkpoints coordinate the cellular response to genotoxic stress and arrest the cell cycle in response to DNA damage and replication fork stalling. Homologous recombination is a ubiquitous pathway for the repair of DNA double-stranded breaks and other checkpoint-inducing lesions. Moreover, homologous recombination is involved in postreplicative tolerance of DNA damage and the recovery of DNA replication after replication fork stalling. Here, we show that the phosphorylation on serines 2, 8, and 14 (S2,8,14) of the Rad55 protein is specifically required for survival as well as for normal growth under genome-wide genotoxic stress. Rad55 is a Rad51 paralog in Saccharomyces cerevisiae and functions in the assembly of the Rad51 filament, a central intermediate in recombinational DNA repair. Phosphorylation-defective rad55-S2,8,14A mutants display a very slow traversal of S phase under DNA-damaging conditions, which is likely due to the slower recovery of stalled replication forks or the slower repair of replication-associated DNA damage. These results suggest that Rad55-S2,8,14 phosphorylation activates recombinational repair, allowing for faster recovery after genotoxic stress.
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Rad55 and Nej1 are examples of repair proteins phosphorylated by checkpoint kinases in budding yeast, and their modification leads to enhanced repair of double-strand breaks.
“Examples of repair proteins that are phosphorylated by checkpoint kinases in budding yeast include Rad55 and Nej1 (3, 21), modification of which leads to enhanced repair of double-strand breaks.”
From A Role for Checkpoint Kinase-Dependent Rad26 Phosphorylation in Transcription-Coupled DNA Repair in <i>Saccharomyces cerevisiae</i> (2010) · cites this paper as [21]
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- Authors
- Herzberg, K., Bashkirov, V. I., Rolfsmeier, M., Haghnazari, E., McDonald, W. H., Anderson, S., Bashkirova, E. V., Yates, J. R., & Heyer, W.-D.
- Affiliations
- University of California, Davis (US)
- Sections of Microbiology
- Scripps Research Institute (US)
- University of California System (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2006-11
- Volume
- 26
- Issue
- 22
- Pages
- 8396-8409
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1636779
- OpenAlex
- W2137627491
- Cited by
- 95
- References
- 83
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 6
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA92276, R01CA092276)
- National Center for Research Resources (RR-11823, P41RR011823)
- 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
- Rad55, protein phosphorylation, homologous recombination, replication fork stalling, DNA damage checkpoint, recombinational DNA repair, genotoxic stress, S phase progression, Saccharomyces cerevisiae
- MeSH terms
- Adenosine Triphosphatases, Amino Acid Sequence, DNA Damage, DNA Repair, DNA Replication, DNA-Binding Proteins, DNA, Fungal, Models, Genetic, Molecular Sequence Data, Phosphorylation, Recombination, Genetic, Saccharomyces cerevisiae, Serine, Mass Spectrometry, Gene Expression Regulation, Fungal, Genome, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Proto-Oncogene Proteins c-raf, Saccharomyces cerevisiae Proteins, DNA Repair Enzymes, Rad52 DNA Repair and Recombination Protein, Checkpoint Kinase 2
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