The human checkpoint sensor Rad9–Rad1–Hus1 interacts with and stimulates NEIL1 glycosylase
Open accessAbstract
The checkpoint protein Rad9/Rad1/Hus1 heterotrimer (the 9-1-1 complex) is structurally similar to the proliferating cell nuclear antigen sliding clamp and has been proposed to sense DNA damage that leads to cell cycle arrest or apoptosis. Human (h) NEIL1 DNA glycosylase, an ortholog of bacterial Nei/Fpg, is involved in repairing oxidatively damaged DNA bases. In this study, we show that hNEIL1 interacts with hRad9, hRad1 and hHus1 as individual proteins and as a complex. Residues 290-350 of hNEIL1 are important for the 9-1-1 association. A significant fraction of the hNEIL1 nuclear foci co-localize with hRad9 foci in hydrogen peroxide treated cells. Human NEIL1 DNA glycosylase activity is significantly stimulated by hHus1, hRad1, hRad9 separately and the 9-1-1 complex. Thus, the 9-1-1 complex at the lesion sites serves as both a damage sensor to activate checkpoint control and a component of base excision repair.
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The 9-1-1 complex interacts with BER proteins APE1, Pol β, FEN1, DNA ligase I, and DNA glycosylases MutY, NEIL1, and TDG, stimulating their DNA repair activities.
“As a critical component of ATR-Chk1 checkpoint pathway, the 9-1-1 complex interacts with several BER proteins: APE1, Polymerase β (Pol β), FEN1, DNA ligase I, as well as DNA glycosylases MutY, NEIL1, and TDG, thereby stimulating their DNA repair activities [177–185] (Fig. 3).”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [183]
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BackgroundInfluentialInduction of the Human Oxidized Base-specific DNA Glycosylase NEIL1 by Reactive Oxygen Species
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- Authors
- Guan, X., Bai, H., Shi, G., Theriot, C. A., Hazra, T. K., Mitra, S., & Lu, A.-L.
- Affiliations
- University of Maryland, Baltimore (US)
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Lu, A-Lien
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-03-29
- Volume
- 35
- Issue
- 8
- Pages
- 2463-2472
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC1885643
- OpenAlex
- W2030121415
- Cited by
- 74
- References
- 70
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 2 · 2016: 3 · 2015: 5 · 2014: 3 · 2013: 9 · 2012: 5
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- University of North Carolina at Chapel Hill
- University of California, Irvine
- National Cancer Institute (CA102271, CA78391, R01CA078391, R01CA102271, R56CA078391, R01CA081063, CA81063)
- National Institute of Environmental Health Sciences (P01 ES 06676, P30ES006676)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- DNA damage recognition, DNA base excision repair, hydrogen peroxide, protein-protein interaction, DNA damage checkpoint, cell cycle arrest
- MeSH terms
- Binding Sites, Cell Line, Enzyme Activation, Exonucleases, Humans, Cell Cycle Proteins, DNA Glycosylases
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