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Human DNA polymerase iota protects cells against oxidative stress
Author(s) -
Petta Tirzah Braz,
Nakajima Satoshi,
Zlatanou Anastasia,
Despras Emmanuelle,
CouvePrivat Sophie,
Ishchenko Alexander,
Sarasin Alain,
Yasui Akira,
Kannouche Patricia
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.210
Subject(s) - biology , oxidative stress , polymerase , dna polymerase , dna , microbiology and biotechnology , polymerase chain reaction , dna damage , oxidative phosphorylation , genetics , gene , biochemistry
Human DNA polymerase iota (polι) is a unique member of the Y‐family of specialised polymerases that displays a 5′deoxyribose phosphate (dRP) lyase activity. Although polι is well conserved in higher eukaryotes, its role in mammalian cells remains unclear. To investigate the biological importance of polι in human cells, we generated fibroblasts stably downregulating polι (MRC5‐polι KD ) and examined their response to several types of DNA‐damaging agents. We show that cell lines downregulating polι exhibit hypersensitivity to DNA damage induced by hydrogen peroxide (H 2 O 2 ) or menadione but not to ethylmethane sulphonate (EMS), UVC or UVA. Interestingly, extracts from cells downregulating polι show reduced base excision repair (BER) activity. In addition, polι binds to chromatin after treatment of cells with H 2 O 2 and interacts with the BER factor XRCC1. Finally, green fluorescent protein‐tagged polι 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 polι in protecting cells from oxidative damage.