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Involvement of Cellular Double-Stranded DNA Break Binding Proteins in Processing of the Recombinant Adeno-Associated Virus Genome

Zentilin, Lorena, Marcello, Alessandro, Giacca, Mauro·2001·Journal of Virology
DOI 10.1128/jvi.75.24.12279-12287.2001
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Abstract

Unlike postmitotic tissues in vivo, transduction of cultured cells is poor with recombinant adeno-associated virus (rAAV). The ability of rAAV to transduce cells is greatly enhanced by a variety of agents that induce DNA damage and is elevated in cells defective in the ataxia telangiectasia gene product (ATM), showing increased genomic instability. Here we show that DNA double-stranded break (DSB) repair pathways are involved in the regulation of rAAV transduction efficiency. By quantitative chromatin immunoprecipitation, we found that Ku86 and Rad52 proteins associate with viral DNA inside transduced cells. Both proteins are known to competitively recognize hairpin structures and DNA termini and to promote repair of DSBs, the former by facilitating nonhomologous end joining and the latter by initiating homologous recombination. We found that rAAV transduction is increased in Ku86-defective cells while it is inhibited in Rad52 knockout cells. These results suggest that binding of Rad52 to the rAAV genome might be involved in processing of the vector genome through a homologous recombination pathway.

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  • hSREBP2 delivery preferentially stimulates the Bloch pathway of cholesterol biosynthesis.

    “hSREBP2 delivery in glial cells, although unable to affect lanosterol and lathosterol levels (Fig. 2H-I), led to a significant increase in desmosterol in the striata of R6/2-hBP2 mice compared with R6/2-Tom mice (Fig. 2J), suggesting a preferential stimulation of the Bloch pathway of cholesterol biosynthesis which is more related to astrocytes 29 (Fig. 2A).”

    From SREBP2 gene therapy targeting striatal astrocytes ameliorates Huntington’s disease phenotypes (2021) · cites this paper as [29]

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Metadata

Authors
Zentilin, L., Marcello, A., & Giacca, M.
Affiliations
<!--label omitted: 1-->Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, 34012 Trieste,1 and
Venue
Journal of Virology
Publisher
American Society for Microbiology
Published
2001-12-15
Volume
75
Issue
24
Pages
12279-12287
ISSN
  • 0022-538X
  • 1098-5514
DOI
10.1128/jvi.75.24.12279-12287.2001
Cited by
101
References
5
Language
en
Licence
journals.asm.org/non-commercial-tdm-license (tdm)

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