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.
authors: Department of Biochemistry and Molecular Biology and Greenebaum Cancer Center, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
authors: Xin
authors: X
authors: Guan
authors: Haibo
authors: H
authors: Bai
authors: Guoli
authors: G
authors: Shi
authors: Corey A
authors: CA
authors: Theriot
authors: Tapas K
authors: TK
authors: Hazra
authors: Sankar
authors: S
authors: Mitra
authors: A-Lien
authors: AL
authors: Lu
mesh_terms: D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism*; D002460:Cell Line; D045647:DNA Glycosylases / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D005092:Exonucleases / Q000032:analysis / Q000378:metabolism*; D006801:Humans
chemical_list: D018797:Cell Cycle Proteins; C549605:HUS1 protein, human; C462949:HUS1B protein, human; C069930:rad9 protein; D005092:Exonucleases; C113574:Rad1 protein, human; D045647:DNA Glycosylases; C473634:NEIL1 protein, human