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R.B. · 07-12-2006, 12:37 PM

Interesting post.

I did a search and found this which links p53 to telomeres.

RB

http://focus.hms.harvard.edu/1999/Ma...99/briefs.html

P53 May Induce Death in Cells with Short Telomeres
As a cell ages, the ends of its chromosomes—the telomeres—are worn away, and the cell receives a signal to stop dividing or die. A study in the May 14 Cell by Lynda Chin and Steven Artandi (colead authors), working in the lab of Ronald DePinho, professor of medicine at Dana-Farber, implicates the tumor supressor p53 in triggering the death of cells with shortened telomeres, and suggests that complete loss of p53 activity combined with some telomere loss can lead to accelerated cancer formation.
Using cells from mouse strains in which the telomeres is shortened to different degrees, the authors found that severe telomere shortening triggers DNA damage checkpoints, activating p53 and causing cell death, senescence, or both. So they explored what would happen in the absence of p53, by creating mice that both have shortened telomeres and lack p53.
Surprisingly, they saw two distinct responses. Progressive telomere shortening usually results in germ cell apoptosis. Removal of p53 prevents apoptosis in animals with partial telomere loss. But in animals with shorter telomeres, germ cell death proceeds whether p53 is there or not. The results suggest that there are two triggers for cell death in response to telomere loss, only one of which is dependent on p53 activity.
These results, together with those showing that telomere-p53-deficient cells are more likely to become cancerous, lead the authors to suggest that lack of p53 permits a cell to pass through an early checkpoint, but lack of telomeric structures eventually causes massive chromosome instability and death for most cells.
In a related article in Cell, members of the DePinho lab report tumor reduction in mice with impaired telomeres but intact p53 activity, further evidence of the need for telomeres in cancer cells and the role of p53 in catching those cancer cells without them.

07-12-2006, 12:37 PM	#3
R.B. Senior Member Join Date: Mar 2006 Posts: 1,843	Interesting post. I did a search and found this which links p53 to telomeres. RB http://focus.hms.harvard.edu/1999/Ma...99/briefs.html P53 May Induce Death in Cells with Short Telomeres As a cell ages, the ends of its chromosomes—the telomeres—are worn away, and the cell receives a signal to stop dividing or die. A study in the May 14 Cell by Lynda Chin and Steven Artandi (colead authors), working in the lab of Ronald DePinho, professor of medicine at Dana-Farber, implicates the tumor supressor p53 in triggering the death of cells with shortened telomeres, and suggests that complete loss of p53 activity combined with some telomere loss can lead to accelerated cancer formation. Using cells from mouse strains in which the telomeres is shortened to different degrees, the authors found that severe telomere shortening triggers DNA damage checkpoints, activating p53 and causing cell death, senescence, or both. So they explored what would happen in the absence of p53, by creating mice that both have shortened telomeres and lack p53. Surprisingly, they saw two distinct responses. Progressive telomere shortening usually results in germ cell apoptosis. Removal of p53 prevents apoptosis in animals with partial telomere loss. But in animals with shorter telomeres, germ cell death proceeds whether p53 is there or not. The results suggest that there are two triggers for cell death in response to telomere loss, only one of which is dependent on p53 activity. These results, together with those showing that telomere-p53-deficient cells are more likely to become cancerous, lead the authors to suggest that lack of p53 permits a cell to pass through an early checkpoint, but lack of telomeric structures eventually causes massive chromosome instability and death for most cells. In a related article in Cell, members of the DePinho lab report tumor reduction in mice with impaired telomeres but intact p53 activity, further evidence of the need for telomeres in cancer cells and the role of p53 in catching those cancer cells without them.