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

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...

Full description

Bibliographic Details
Main Authors:	Guan, Xin, Bai, Haibo, Shi, Guoli, Theriot, Corey A., Hazra, Tapas K., Mitra, Sankar, Lu, A-Lien
Format:	Online
Language:	English
Published:	Oxford University Press 2007
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885643/

id	pubmed-1885643
recordtype	oai_dc
spelling	pubmed-18856432007-06-07 The human checkpoint sensor Rad9–Rad1–Hus1 interacts with and stimulates NEIL1 glycosylase Guan, Xin Bai, Haibo Shi, Guoli Theriot, Corey A. Hazra, Tapas K. Mitra, Sankar Lu, A-Lien Nucleic Acid Enzymes 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. Oxford University Press 2007-04 2007-03-29 /pmc/articles/PMC1885643/ /pubmed/17395641 http://dx.doi.org/10.1093/nar/gkm075 Text en © 2007 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Guan, Xin Bai, Haibo Shi, Guoli Theriot, Corey A. Hazra, Tapas K. Mitra, Sankar Lu, A-Lien
spellingShingle	Guan, Xin Bai, Haibo Shi, Guoli Theriot, Corey A. Hazra, Tapas K. Mitra, Sankar Lu, A-Lien The human checkpoint sensor Rad9–Rad1–Hus1 interacts with and stimulates NEIL1 glycosylase
author_facet	Guan, Xin Bai, Haibo Shi, Guoli Theriot, Corey A. Hazra, Tapas K. Mitra, Sankar Lu, A-Lien
author_sort	Guan, Xin
title	The human checkpoint sensor Rad9–Rad1–Hus1 interacts with and stimulates NEIL1 glycosylase
title_short	The human checkpoint sensor Rad9–Rad1–Hus1 interacts with and stimulates NEIL1 glycosylase
title_full	The human checkpoint sensor Rad9–Rad1–Hus1 interacts with and stimulates NEIL1 glycosylase
title_fullStr	The human checkpoint sensor Rad9–Rad1–Hus1 interacts with and stimulates NEIL1 glycosylase
title_full_unstemmed	The human checkpoint sensor Rad9–Rad1–Hus1 interacts with and stimulates NEIL1 glycosylase
title_sort	human checkpoint sensor rad9–rad1–hus1 interacts with and stimulates neil1 glycosylase
description	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.
publisher	Oxford University Press
publishDate	2007
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885643/
_version_	1611396916539555840

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

Similar Items