Increased gene amplification in immortalized rodent cell lines deficient in the catalytic subunit of the DNA-dependent protein kinase (Articolo in rivista)

Type
Label
  • Increased gene amplification in immortalized rodent cell lines deficient in the catalytic subunit of the DNA-dependent protein kinase (Articolo in rivista) (literal)
Anno
  • 2001-01-01T00:00:00+01:00 (literal)
Alternative label
  • Mondello C., Rebuzzini P., Dolzan M., Edmonson S., Taccioli G., Giulotto E. (2001)
    Increased gene amplification in immortalized rodent cell lines deficient in the catalytic subunit of the DNA-dependent protein kinase
    in Cancer research (Chic. Ill.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Mondello C., Rebuzzini P., Dolzan M., Edmonson S., Taccioli G., Giulotto E. (literal)
Pagina inizio
  • 4520 (literal)
Pagina fine
  • 4525 (literal)
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  • Pubblicazione su rivista ISI con elevato IF: 8.3 (literal)
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  • 61 (literal)
Rivista
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  • In questo lavoro viene dimostrato che cellule di roditore difettive nel gene per la DNA-PKcs, un enzima coinvolto nella riparazione delle rotture a doppia elica, presentano un aumentato tasso di amplificazione genica. Questo risultato consente di dimostrare una stretta relazione tra rotture a doppia elica, riparazione del DNA ed amplifcazione genica e dà informazioni sui meccanismi coinvolti in questo processo. (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • C. Mondello , P. Rebuzzini, M. Dolzan: Istituto di Genetica Molecolare, CNR, Pavia; S. Edmonson , G. Taccioli: School of Medicine, Università di Boston; E. Giulotto: Dipartimento di Genetica e Microbiologia, Università di Pavia. (literal)
Titolo
  • Increased gene amplification in immortalized rodent cell lines deficient in the catalytic subunit of the DNA-dependent protein kinase (literal)
Abstract
  • Gene amplification is one of the most frequent genome anomalies observed in tumor cells, while it has never been detected in cells of normal origin. A large body of evidence indicates that DNA double-strand breaks (DSBs) play a key role in initiating gene amplification. In mammals, DSBs are mainly repaired through the non-homologous end joining pathway (NHEJ) that requires a functional DNA-dependent protein kinase catalytic subunit (DNA-PKcs). In rodent cell lines, PALA resistance is considered a measure of gene amplification since it is mainly due to amplification of the CAD (carbamyl-P-synthetase, aspartate transcarbamilase, dihydro-orotase) gene. In this paper we show that the radiosensitive hamster cell line V3, which is defective in DSB repair because of a mutation in the DNA-PKcs gene, displays also an increased frequency of gene amplification. In these cells we found that the amplification of the CAD gene occurs with a frequency and a rate more than one order of magnitude higher than in control cell lines, although it relies on the same mechanisms. When the same analysis was performed in mouse embryo fibroblasts (MEFs) obtained from animals in which the DNA-PKcs gene was ablated by homologous recombination, a higher frequency of amplification compared to the controls was found only after cellular immortalization. In primary DNA-PKcs-/- MEFs, PALA treatment induced a block in the cell cycle and no PALA resistant clones were found. Our results indicate that the lack of DNA-PKcs increases the probability that gene amplification occurs in a genetic background already permissive, like that of immortalized cells, while is not sufficient to make normal cells able to amplify. (literal)
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