Details

Autor(en) / Beteiligte

• Borel, Franck
• Lohez, Olivier D.
• Lacroix, Françoise B.
• Margolis, Robert L.

Titel

Multiple Centrosomes Arise from Tetraploidy Checkpoint Failure and Mitotic Centrosome Clusters in p53 and RB Pocket Protein-Compromised Cells

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2002-07, Vol.99 (15), p.9819-9824

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2002

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• A high degree of aneuploidy characterizes the majority of human tumors. Aneuploid status can arise through mitotic or cleavage failure coupled with failure of tetraploid G1checkpoint control, or through deregulation of centrosome number, thus altering the number of mitotic spindle poles. p53 and the RB pocket proteins are important to the control of G1progression, and p53 has previously been suggested as important to the control of centrosome duplication. We demonstrate here that neither suppression of p53 nor of the RB pocket protein family directly generates altered centrosome numbers in any of several mammalian primary cell lines. Instead, amplification of centrosome number occurs in two steps. The first step is failure to arrest at a G1tetraploidy checkpoint after failure to segregate the genome in mitosis, and the second step is clustering of centrosomes at a single spindle pole in subsequent tetraploid or aneuploid mitosis. The trigger for these events is mitotic or cleavage failure that is independent of p53 or RB status. Finally, we find that mouse embryo fibroblasts spontaneously enter tetraploid G1, explaining the previous demonstration of centrosome amplification by p53 abrogation alone in these cells.