Exploring DNA damage responses in human cells with recombinant adenoviral vectors.
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.
Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
Melissa G
MG
Armelini
Keronninn M
KM
Lima-Bessa
Maria Carolina N
MC
Marchetto
Alysson R
AR
Muotri
Vanessa
V
Chiganças
Ricardo A
RA
Leite
Helotonio
H
Carvalho
Carlos F M
CF
Menck
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D049914:DNA Repair-Deficiency Disorders / Q000235:genetics; D020868:Gene Silencing; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011995:Recombination, Genetic; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D014161:Transduction, Genetic / Q000379:methods; D014466:Ultraviolet Rays / Q000009:adverse effects; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000473:pathology / Q000628:therapy