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Exploring DNA damage responses in human cells with recombinant adenoviral vectors

Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1374, 05508-900 Sao Paulo, SP, Brazil

Keronninn M. Lima-Bessa

Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1374, 05508-900 Sao Paulo, SP, Brazil

Maria Carolina N. Marchetto

Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA

Alysson R. Muotri

Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA

Vanessa Chiganças

CNRS UPR-2169, Institut Gustave Roussy PR2, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

Ricardo A. Leite

Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1374, 05508-900 Sao Paulo, SP, Brazil

Helotonio Carvalho

Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1374, 05508-900 Sao Paulo, SP, Brazil

Carlos F. M. Menck

Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1374, 05508-900 Sao Paulo, SP, Brazil, cfmmenck{at}usp.br

Recombinant adenoviral vectors provide efficient means for gene transduction in mammalian cells in vitro and in vivo. We are currently using these vectors to transduce DNA repair genes into repair deficient cells, derived from xeroderma pigmentosum (XP) patients. XP is an autosomal syndrome characterized by a high frequency of skin tumors, especially in areas exposed to sunlight, and, occasionally, developmental and neurological abnormalities. XP cells are deficient in nucleotide excision repair (affecting one of the seven known XP genes, xpa to xpg) or in DNA replication of DNA lesions (affecting DNA polymerase eta, xpv). The adenovirus approach allows the investigation of different consequences of DNA lesions in cell genomes. Adenoviral vectors carrying several xp and photolyases genes have been constructed and successfully tested in cell culture systems and in vivo directly in the skin of knockout model mice. This review summarizes these recent data and proposes the use of recombinant adenoviruses as tools to investigate the mechanisms that provide protection against DNA damage in human cells, as well as to better understand the higher predisposition of XP patients to cancer. Human & Experimental Toxicology (2007) 26, 899—906

Key Words: adenoviral vectors • DNA damage • DNA repair • ultraviolet • xeroderma pigmentosum

Human & Experimental Toxicology, Vol. 26, No. 11, 899-906 (2007)
DOI: 10.1177/0960327107083556


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