Chromosomal end-to-end fusions in immortalized mouse embryonic fibroblasts deficient in the DNA-dependent protein kinase catalytic subunit.

Abstract:

:Telomeres constitute the ends of the linear eukaryotic chromosomes and are essential for the maintenance of chromosome stability and genome integrity. One of the consequences of an altered telomere structure is the formation of telomeric fusions (TFs), that is aberrant chromosomes in which two elements are fused at their telomeres. Proteins involved in the non-homologous end joining pathway for the repair of the DNA double strand breaks, as the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), contribute to the formation of a functional telomere. To investigate the role of DNA-PKcs in telomere functionality, we studied the frequency of TFs in mouse embryonic fibroblasts obtained from animals in which the DNA-PKcs gene had been inactivated; the analysis was performed prior and after spontaneous immortalization in culture. Our results suggest that DNA-PKcs deficiency has a limited effect, if any, on TF formation in primary cells, while it further increases chromosomal instability in immortalized cells. In fact, the frequency of TFs was significantly higher in immortalized DNA-PKcs mutant cells compared to wild type cells. Together with TFs, we also found metacentric or submetacentric chromosomes in which no telomeric sequences were detected at the joining site. The frequency of this anomaly, that resembles the Robertsonian translocations observed in wild mice, was independent of the DNA-PKcs genotype. This suggests that the formation of these rearranged chromosomes does not rely on a functional DNA-PKcs.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Rebuzzini P,Lisa A,Giulotto E,Mondello C

doi

10.1016/j.canlet.2003.08.028

keywords:

subject

Has Abstract

pub_date

2004-01-08 00:00:00

pages

79-86

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304383503005469

journal_volume

203

pub_type

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