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Recruitment of Mec1 and Ddc1 Checkpoint Proteins to Double-Strand Breaks Through Distinct Mechanisms
Abstract
In response to DNA damage, eukaryotic cells activate checkpoint pathways that arrest cell cycle progression and induce the expression of genes required for DNA repair. In budding yeast, the homothallic switching (HO) endonuclease creates a site-specific double-strand break at the mating type ( MAT ) locus. Continuous HO expression results in the phosphorylation of Rad53, which is dependent on products of the ataxia telangiectasia mutated–related MEC1 gene and other checkpoint genes, including DDC1 , RAD9 , and RAD24 . Chromatin immunoprecipitation experiments revealed that the Ddc1 protein associates with a region near the MAT locus after HO expression. Ddc1 association required Rad24 but not Mec1 or Rad9. Mec1 also associated with a region near the cleavage site after HO expression, but this association is independent of Ddc1, Rad9, and Rad24. Thus, Mec1 and Ddc1 are recruited independently to sites of DNA damage, suggesting the existence of two separate mechanisms involved in recognition of DNA damage.
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“The ATR-ATRIP complex and 9-1-1 complexes are recruited to RPA-ssDNA independently and are bridged by the multiple-function protein TopBP1 (Topoisomerase IIβ binding protein 1) [106–110].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [106]
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Metadata
- Authors
- Kondo, T., Wakayama, T., Naiki, T., Matsumoto, K., & Sugimoto, K.
- Affiliations
- Nagoya University (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Kondo, Tae
- Wakayama, Tatsushi
- Naiki, Takahiro
- Sugimoto, Katsunori
- Venue
- Science
- Published
- 2001-10-26
- Volume
- 294
- Issue
- 5543
- Pages
- 867-870
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2014438192
- Cited by
- 258
- References
- 25
- Citations by year
- 2026: 3 · 2025: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 8 · 2013: 3 · 2012: 4
- FWCI
- 12.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- 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
- Mec1, DNA damage checkpoint, DNA double-strand breaks, Rad53 phosphorylation, HO endonuclease, mating-type locus, Rad24, Rad9, DNA damage recognition, Saccharomyces cerevisiae
- MeSH terms
- Mating Factor, Cell Cycle, Cell Nucleus, Cytoplasm, DNA Damage, DNA Repair, DNA-Binding Proteins, DNA, Fungal, Saccharomycetales, Fungal Proteins, Genes, Fungal, Mutation, Nuclear Proteins, Peptides, Phosphorylation, Recombinant Fusion Proteins, Recombination, Genetic, Transformation, Genetic, Deoxyribonucleases, Type II Site-Specific, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Genes, cdc, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Genes, Mating Type, Fungal, Checkpoint Kinase 2
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