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Titolo:
A NEW CONCEPT IN (ADENOVIRAL) ONCOGENESIS - INTEGRATION OF FOREIGN DNA AND ITS CONSEQUENCES
Autore:
DOERFLER W;
Indirizzi:
UNIV COLOGNE,INST GENET,WEYERTAL 121 D-50931 COLOGNE GERMANY
Titolo Testata:
Biochimica et biophysica acta, CR. Reviews on cancer
fascicolo: 2, volume: 1288, anno: 1996,
pagine: 79 - 99
SICI:
0304-419X(1996)1288:2<79:ANCI(O>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAJOR LATE PROMOTER; PRODUCTIVELY INFECTED-CELLS; GENOMIC SEQUENCING REVEALS; VIRAL GENE-EXPRESSION; TUMOR-SUPPRESSOR GENE; ADENOVIRUS-TYPE-12 DNA; HAMSTER-CELLS; NUCLEOTIDE-SEQUENCE; INTRACELLULAR FORMS; TRANSFORMED-CELLS;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
111
Recensione:
Indirizzi per estratti:
Citazione:
W. Doerfler, "A NEW CONCEPT IN (ADENOVIRAL) ONCOGENESIS - INTEGRATION OF FOREIGN DNA AND ITS CONSEQUENCES", Biochimica et biophysica acta, CR. Reviews on cancer, 1288(2), 1996, pp. 79-99

Abstract

A new concept for viral oncogenesis is presented which is based on experimental work on the chromosomal integration of adenovirus DNA into mammalian genomes. The mechanism of adenovirus DNA integration is akinto non-sequence-specific insertional recombination in which patch homologies between the recombination partners ate frequently observed. This reaction has been imitated in a cell-free system by using nuclear extracts from hamster cells and pal-try purified fractions derived fromthem. As a consequence of foreign DNA insertion into the mammalian genome, the foreign DNA is extensively de novo methylated in specific patterns, presumably as part of a mammalian host cell defense mechanism against inserted foreign DNA which can be permanently silenced in thisway. A further corollary of foreign (adenovirus or bacteriophage lambda) DNA integration is seen in extensive changes in cellular DNA methylation patterns at sites far remote from the locus of insertional recombination. Repetitive cellular, retrotransposon-like sequences are particularly, but not exclusively, prone to these increases in DNA methylation. It is conceivable that these changes in DNA methylation are a reflection of a profound overall reorganization process in the affectedgenomes. Could these alterations significantly contribute to the transformation events during viral or other types of oncogenesis? These sequelae of foreign DNA integration into established mammalian genomes will have to be critically considered when interpreting results obtained with transgenic, knock-out, and knock-in animals and when devising schemes for human somatic gene therapy. The interpretation of de novo methylation as a cellular defense mechanism has prompted investigationson the fate of food-ingested foreign DNA. The gastrointestinal (GI) tract provides a large surface for the entry of foreign DNA into any organism. As a tracer molecule, bacteriophage M13 DNA has been fed to mice. Fragments of this DNA can be found in small amounts (about 1% of the administered DNA) in all parts of the intestinal tract and in the feces. Furthermore, M13 DNA can be traced in the columnar epithelia of the intestine, in Peyer's plaque leukocytes, in peripheral white bloodcells, in spleen, and liver. Authentic M13 DNA has been recloned fromtotal spleen DNA. If integrated, this DNA might elicit some of the described consequences of foreign DNA insertion into the mammalian genome. Food-ingested DNA will likely infiltrate the organism more frequently than viral DNA.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 21:39:58