The DNA repair complex Ku70/86 modulates Apaf1 expression upon DNA damage

D. De Zio, M. Bordi, E. Tino, C. Lanzuolo, E. Ferraro, E. Mora, F. Ciccosanti, G. M. Fimia, V. Orlando, F. Cecconi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Apaf1 is a key regulator of the mitochondrial intrinsic pathway of apoptosis, as it activates executioner caspases by forming the apoptotic machinery apoptosome. Its genetic regulation and its post-translational modification are crucial under the various conditions where apoptosis occurs. Here we describe Ku70/86, a mediator of non-homologous end-joining pathway of DNA repair, as a novel regulator of Apaf1 transcription. Through analysing different Apaf1 promoter mutants, we identified an element repressing the Apaf1 promoter. We demonstrated that Ku70/86 is a nuclear factor able to bind this repressing element and downregulating Apaf1 transcription. We also found that Ku70/86 interaction with Apaf1 promoter is dynamically modulated upon DNA damage. The effect of this binding is a downregulation of Apaf1 expression immediately following the damage to DNA; conversely, we observed Apaf1 upregulation and apoptosis activation when Ku70/86 unleashes the Apaf1-repressing element. Therefore, besides regulating DNA repair, our results suggest that Ku70/86 binds to the Apaf1 promoter and represses its activity. This may help to inhibit the apoptosome pathway of cell death and contribute to regulate cell survival.

Original languageEnglish (US)
Pages (from-to)516-527
Number of pages12
JournalCell Death and Differentiation
Issue number3
StatePublished - Mar 2011
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements. F Cecconi is supported by grants from the Telethon Foundation, AIRC, the Italian Ministry of Health and the Italian Ministry of University and Research. D De Zio is supported by a fellowship from the Telethon Foundation. The authors thank M Acuna Villa and MW Bennett for editorial and secretarial work, F Florenzano and G Filomeni for research assistance, and A Nobili for technical support.


  • apoptosis
  • apoptosome
  • transcriptional regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'The DNA repair complex Ku70/86 modulates Apaf1 expression upon DNA damage'. Together they form a unique fingerprint.

Cite this