Journal Article

DNA double-strand breaks trigger apoptosis in p53-deficient fibroblasts

Jochen Lips and Bernd Kaina

in Carcinogenesis

Volume 22, issue 4, pages 579-585
Published in print April 2001 | ISSN: 0143-3334
Published online April 2001 | e-ISSN: 1460-2180 | DOI:
DNA double-strand breaks trigger apoptosis in p53-deficient fibroblasts

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  • Clinical Cytogenetics and Molecular Genetics


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DNA double-strand breaks (DSBs) are induced by ionizing radiation (IR) and various radiomimetic agents directly, or indirectly as a consequence of DNA repair, recombination and replication of damaged DNA. They are ultimately involved in the generation of chromosomal aberrations and were reported to cause genomic instability, gene amplification and reproductive cell death. To address the question of whether DSBs act as a trigger of apoptosis, we induced DSBs by means of restriction enzyme electroporation and compared the effect with IR in mouse fibroblasts that differ in p53 status [wild-type (+/+) versus p53-deficient (–/–) cells]. We show that (i) electroporation of PvuII is highly efficient in the induction of DSBs, (ii) electroporation of PvuII increases the rate of apoptosis, but not of necrosis in p53–/– cells, (iii) treatment with γ-rays induces both apoptosis and necrosis in p53–/– cells, (iv) the frequency of DSBs correlates with the yield of apoptosis and (v) both PvuII and γ-ray treatment reduce the level of anti-apoptotic Bcl-2 protein in p53–/– cells whereas the level of Bax remains unaltered. Cells expressing wild-type p53 were more resistant than p53-deficient cells as to the induction of apoptosis and did not show Bcl-2 decline upon treatment with PvuII and γ-rays. The data provide evidence that blunt-ended DSBs induced by restriction enzyme PvuII act as a highly efficient trigger of apoptosis, but not of necrosis. This process is related to Bcl-2 decline and does not require p53.

Keywords: DSBs, DNA double-strand breaks; IR, ionizing radiation; SCGE, single cell gel electrophoresis.

Journal Article.  5276 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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