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

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

Research output: Contribution to journalArticle

54 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2463-2472
Number of pages10
JournalNucleic Acids Research
Volume35
Issue number8
DOIs
StatePublished - Apr 2007

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DNA Glycosylases
Proliferating Cell Nuclear Antigen
Cell Cycle Checkpoints
DNA Repair
Hydrogen Peroxide
DNA Damage
Apoptosis
DNA
Proteins
rad9 protein

ASJC Scopus subject areas

  • Genetics

Cite this

The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase. / Guan, Xin; Bai, Haibo; Shi, Guoli; Theriot, Corey A.; Hazra, Tapas; Mitra, Sankar; Lu, A. Lien.

In: Nucleic Acids Research, Vol. 35, No. 8, 04.2007, p. 2463-2472.

Research output: Contribution to journalArticle

Guan, Xin ; Bai, Haibo ; Shi, Guoli ; Theriot, Corey A. ; Hazra, Tapas ; Mitra, Sankar ; Lu, A. Lien. / The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase. In: Nucleic Acids Research. 2007 ; Vol. 35, No. 8. pp. 2463-2472.
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