The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase

Xin Guan; Haibo Bai; Guoli Shi; Corey A. Theriot; Tapas K. Hazra; Sankar Mitra; A. Lien Lu

doi:10.1093/nar/gkm075

The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase

Xin Guan, Haibo Bai, Guoli Shi, Corey A. Theriot, Tapas K. Hazra, Sankar Mitra, A. Lien Lu

Internal Medicine

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	2463-2472
Number of pages	10
Journal	Nucleic acids research
Volume	35
Issue number	8
DOIs	https://doi.org/10.1093/nar/gkm075
State	Published - Apr 2007

ASJC Scopus subject areas

Genetics

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10.1093/nar/gkm075

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@article{1b223328c19a494ba1a166b549bc1210,

title = "The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase",

abstract = "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.",

author = "Xin Guan and Haibo Bai and Guoli Shi and Theriot, {Corey A.} and Hazra, {Tapas K.} and Sankar Mitra and Lu, {A. Lien}",

note = "Funding Information: We thank Drs Evan Y. Lee (University of California, Irvine, CA, USA) and Alan E. Tomkinson (University of Maryland, Baltimore, MD, USA) for kindly providing the plasmids. We thank Drs. Alan E. Tomkinson and Aziz Sancar (University of North Carolina at Chapel Hill, NC, USA) for providing the baculovirus vectors. We appreciate Dr Howard Lieberman (Columbia University, NY, USA) for kindly supplying the 9-1-1 proteins for the initial work and thank Dr Susan Wallace (University of Vermont, VT, USA) for the DNA substrate. This work was supported by National Institute of Health grants CA78391 to AL, CA81063 to SM, and CA102271 and P01ES06676 to TKH. Funding to pay the Open Access publication charges for this article was provided by CA78391.",

year = "2007",

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doi = "10.1093/nar/gkm075",

language = "English (US)",

volume = "35",

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T1 - The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase

AU - Guan, Xin

AU - Bai, Haibo

AU - Shi, Guoli

AU - Theriot, Corey A.

AU - Hazra, Tapas K.

AU - Mitra, Sankar

AU - Lu, A. Lien

N1 - Funding Information: We thank Drs Evan Y. Lee (University of California, Irvine, CA, USA) and Alan E. Tomkinson (University of Maryland, Baltimore, MD, USA) for kindly providing the plasmids. We thank Drs. Alan E. Tomkinson and Aziz Sancar (University of North Carolina at Chapel Hill, NC, USA) for providing the baculovirus vectors. We appreciate Dr Howard Lieberman (Columbia University, NY, USA) for kindly supplying the 9-1-1 proteins for the initial work and thank Dr Susan Wallace (University of Vermont, VT, USA) for the DNA substrate. This work was supported by National Institute of Health grants CA78391 to AL, CA81063 to SM, and CA102271 and P01ES06676 to TKH. Funding to pay the Open Access publication charges for this article was provided by CA78391.

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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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JO - Nucleic acids research

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ER -

The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase

Abstract

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