Article
- The EMBO Journal (2008) 27, 2883 - 2895
- doi:10.1038/emboj.2008.210
Published online: 16 October 2008
Subject Category:
Human DNA polymerase iota protects cells against oxidative stress
Tirzah Braz Petta1, Satoshi Nakajima2, Anastasia Zlatanou1, Emmanuelle Despras1, Sophie Couve-Privat3, Alexander Ishchenko3, Alain Sarasin1, Akira Yasui2 and Patricia Kannouche1
- Centre National de la Recherche Scientifique (CNRS) FRE2939, Unit of genetic stability and oncogenesis, Institut Gustave Roussy, Université Paris-Sud, Villejuif, France
- Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
- Centre National de la Recherche Scientifique (CNRS) UMR8126, Unit of molecular interactions and cancer, Institut Gustave Roussy, Université Paris-Sud, Villejuif, France
Correspondence to:
Patricia Kannouche, Centre National de la Recherche Scientifique (CNRS) FRE2939, Institut Gustave Roussy, Université Paris-Sud, PR2, Villejuif 94805 Cedex, France. Tel.: +33 1 4211 4030; Fax: +33 1 4211 5008; E-mail: kannouche@igr.fr
Received 28 April 2008; Accepted 15 September 2008
Abstract
Human DNA polymerase iota (pol
) is a unique member of the Y-family of specialised polymerases that displays a 5'deoxyribose phosphate (dRP) lyase activity. Although pol is well conserved in higher eukaryotes, its role in mammalian cells remains unclear. To investigate the biological importance of pol in human cells, we generated fibroblasts stably downregulating pol (MRC5-polKD) and examined their response to several types of DNA-damaging agents. We show that cell lines downregulating pol exhibit hypersensitivity to DNA damage induced by hydrogen peroxide (H2O2) or menadione but not to ethylmethane sulphonate (EMS), UVC or UVA. Interestingly, extracts from cells downregulating pol show reduced base excision repair (BER) activity. In addition, pol binds to chromatin after treatment of cells with H2O2 and interacts with the BER factor XRCC1. Finally, green fluorescent protein-tagged pol accumulates at the sites of oxidative DNA damage in living cells. This recruitment is partially mediated by its dRP lyase domain and ubiquitin-binding domains. These data reveal a novel role of human pol in protecting cells from oxidative damage.
Keywords:
- BER,
- DNA polymerase,
- oxidative DNA damage,
- Y-family polymerase
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
DNA polymerases and somatic hypermutation of immunoglobulin genes
EMBO reports Review (01 Dec 2005)
NEWS AND VIEWS
Nature Cell Biology News and Views (01 Jun 2006)
DNA polymerases lose their grip
Nature Structural Biology News and Views (01 Nov 2001)
RESEARCH
Controlling the subcellular localization of DNA polymerases ι and η via interactions with ubiquitin
The EMBO Journal Article (21 Jun 2006)
The EMBO Journal Article (15 Nov 2002)
