Details

Autor(en) / Beteiligte

• Mouhamad, Shahul
• Galluzzi, Lorenzo
• Zermati, Yael
• Castedo, Maria
• Kroemer, Guido

Titel

Apaf-1 Deficiency Causes Chromosomal Instability

Ist Teil von

• Cell cycle (Georgetown, Tex.), 2007-12, Vol.6 (24), p.3103-3107

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2007

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Apaf-1 is an essential component of the apoptosome, the molecular complex assembled in response to mitochondrial cytochrome c release that promotes caspase activation. Apaf-1 expression is suppressed in some malignant tumors, in particular melanoma as well as cervical and colorectal carcinoma, in which the loss of Apaf-1 expression marks tumor progression and poor prognosis. Recent results from our laboratory demonstrate that Apaf-1 has an apoptosis-unrelated function that may well account for its role as a tumor suppressor. The knockout of apaf-1 (in mice), the knockdown of Apaf-1 (in human cells) and loss of function mutations of ced-4 (the Caenorhabditis elegans ortholog of Apaf-1) compromise the arrest of DNA synthesis in response to DNA damage, in a context in which apoptosis does not occur. Here, we show that the depletion of Apaf-1 also sensitizes cells to chromosomalinstability induced by different types of DNA damage such as cisplatin, UVC light and γ-irradiation. These results unravel a hitherto unsuspected role for Apaf-1 in the maintenance of genomic stability, independently from its function in the cell death machinery.