The non-homologous end-joining protein Nej1p is a target of the DNA damage checkpoint
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DNA double-strand breaks (DSBs), which are generated by ionizing radiation (IR) and a range of other DNA damaging agents, are repaired by homologous recombination (HR) or non-homologous end-joining (NHEJ). Previous studies have shown that NHEJ in Saccharomyces cerevisiae requires the Yku70p-Yku80p heterodimer and a complex consisting of DNA Ligase IV, Lif1p and Nej1p. Here, we report that Nej1p is phosphorylated in response to DNA damage in a manner that relies on the DNA damage checkpoint kinases Mec1p, Rad53p and Dun1p. By using a mutational approach, we have identified a consensus Dun1p phosphorylation site in Nej1p, and mutation of conserved serine residues within it leads to decreased NHEJ efficiency. These data, together with previous findings that Rad55p--a protein involved in HR--is phosphorylated analogously, point to there being a broad signalling network connecting DNA damage checkpoint responses with the regulation of DNA DSB repair activities.
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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 [4]
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 [3]
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References 39 · Cited by 41
- Authors
- Ahnesorg, P., & Jackson, S. P.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Jackson, Stephen P.
- ORCID
- Jackson, Stephen P.
- Venue
- DNA Repair
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 6
- Issue
- 2
- Pages
- 190-201
- ISSN
- 1568-7856 (ISSN-L)
- 1568-7864
- PMC
- PMC3338008
- OpenAlex
- W2021347463
- Cited by
- 41
- References
- 39
- Citations by year
- 2021: 3 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 4 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- DNA repair (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Research UK (A1672, A3121)
- 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
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- non-homologous end joining, DNA damage checkpoint, protein phosphorylation, DNA double-strand break repair, DNA ligase IV, homologous recombination, Saccharomyces cerevisiae
- MeSH terms
- Amino Acid Sequence, Binding Sites, Cell Nucleus, DNA Repair, DNA-Binding Proteins, Genetic Complementation Test, Molecular Sequence Data, Phosphorylation, Protein Kinases, Recombinant Proteins, Recombination, Genetic, Saccharomyces cerevisiae, Serine, Signal Transduction, Mutagenesis, Site-Directed, Protein Serine-Threonine Kinases, Sequence Homology, Amino Acid, Cell Cycle Proteins, Amino Acid Substitution, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, DNA Breaks, Double-Stranded, Checkpoint Kinase 2
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