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PMID: 17395641 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Nucleic acids research ·Vol. 35 ·No. 8 ·2007-00-00 ·Pages 2463-72

Guan X, Bai H, Shi G, Theriot CA, Hazra TK, Mitra S, Lu AL

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.

MeSH Terms
Binding Sites Cell Cycle Proteins/analysis,metabolism Cell Line DNA Glycosylases/analysis,chemistry,metabolism Enzyme Activation Exonucleases/analysis,metabolism Humans
Chemicals
Cell Cycle Proteins HUS1 protein, human HUS1B protein, human rad9 protein Exonucleases Rad1 protein, human DNA Glycosylases NEIL1 protein, human
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Guan Xin
Department of Biochemistry and Molecular Biology and Greenebaum Cancer Center, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Bai Haibo
Shi Guoli
Theriot Corey A
Hazra Tapas K
Mitra Sankar
Lu A-Lien
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkm075
Published
2007-00-00
Epub
2007-00-29
Pages
2463-72
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1885643
Subset
IM
Grants
NCI NIH HHS · R56 CA078391 · United States
NCI NIH HHS · R01 CA081063 · United States
NCI NIH HHS · CA102271 · United States
NCI NIH HHS · CA78391 · United States
NCI NIH HHS · CA81063 · United States
NIEHS NIH HHS · P01ES06676 · United States
NCI NIH HHS · R01 CA102271 · United States
NIEHS NIH HHS · P30 ES006676 · United States
NCI NIH HHS · R01 CA078391 · United States
External Links
PubMed source DOI: 10.1093/nar/gkm075 PMC Full Text View journal details
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