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Titolo:
Loss of ATM function enhances recombinant adeno-associated virus transduction and integration through pathways similar to UV irradiation
Autore:
Sanlioglu, S; Benson, P; Engelhardt, JF;
Indirizzi:
Univ Iowa, Sch Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 nat & Cell Biol, Iowa City, IA 52242 USA Univ Iowa, Sch Med, Dept Internal Med, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 pt Internal Med, Iowa City, IA 52242 USA Univ Iowa, Sch Med, Ctr Gene Therapy, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 tr Gene Therapy, Iowa City, IA 52242 USA Univ Iowa, Sch Med, Dept Otolaryngol, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 ept Otolaryngol, Iowa City, IA 52242 USA
Titolo Testata:
VIROLOGY
fascicolo: 1, volume: 268, anno: 2000,
pagine: 68 - 78
SICI:
0042-6822(20000301)268:1<68:LOAFER>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-CYCLE CHECKPOINT; ADENOASSOCIATED VIRUS; ATAXIA-TELANGIECTASIA; TYROSINE PHOSPHORYLATION; ULTRAVIOLET-RADIATION; TRANSGENE EXPRESSION; NONDIVIDING CELLS; GENE-EXPRESSION; DNA INTEGRATION; HIGH-FREQUENCY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Engelhardt, JF Univ Iowa, Sch Med, Dept Anat & Cell Biol, 51 Newton Rd,Room 1-111 BSB, Iowa City, IA 52242 USA Univ Iowa 51 Newton Rd,Room 1-111 BSB Iowa City IA USA 52242
Citazione:
S. Sanlioglu et al., "Loss of ATM function enhances recombinant adeno-associated virus transduction and integration through pathways similar to UV irradiation", VIROLOGY, 268(1), 2000, pp. 68-78

Abstract

Ataxia telangiectasia is caused by a genetic defect in the ATM gene that results in altered cellular sensitivity to DNA-damaging agents such as gamma-irradiation. ATM deficiency is associated with an increased incidence of neurological disorders, immune deficiency, and cancer. In this report we demonstrate that recombinant adeno-associated virus (rAAV) gene transfer in ATM-deficient fibroblasts is significantly enhanced over normal fibroblast: cell lines. This enhancement of rAAV transduction in AT cells is correlated with an increased abundance of circular form rAAV genomes, as well as a higher number of integrated head-to-tail concatamer proviral genomes. Studies evaluating AAV trafficking using Cy3-labeled virus suggest that a nuclear mechanism is responsible for increased rAAV transduction in AT cells, because binding, endocytosis, and nuclear trafficking of virus are unaffected by the AT phenotype. Additionally, the profile of rAAV transduction after UV irradiation is significantly blunted in AT cells, suggesting that: the levelof DNA repair enzymes normally associated with UV augmentation of viral transduction may already be maximally elevated. These results further expand our understanding of genes involved in rAAV transduction. (C) 2000 AcademicPress.

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Documento generato il 12/07/20 alle ore 07:46:15