Publikationsdatum:
1999-02-26
Beschreibung:
Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that this suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2). Inhibition of TRF2 resulted in apoptosis in a subset of mammalian cell types. The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, indicating that telomeres lacking TRF2 directly signal apoptosis, possibly because they resemble damaged DNA. Thus, in some cells, telomere shortening may signal cell death rather than senescence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karlseder, J -- Broccoli, D -- Dai, Y -- Hardy, S -- de Lange, T -- GM49046/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Feb 26;283(5406):1321-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA. Cell Genesys, Foster City, CA 94405, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10037601" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Adenoviridae/genetics/physiology
;
Animals
;
*Apoptosis
;
Ataxia Telangiectasia/pathology
;
Ataxia Telangiectasia Mutated Proteins
;
B-Lymphocytes/cytology
;
Cell Cycle Proteins
;
Cell Line
;
Cells, Cultured
;
Cloning, Molecular
;
DNA Damage
;
DNA-Binding Proteins/chemistry/genetics/*physiology
;
Genetic Vectors
;
Humans
;
In Situ Nick-End Labeling
;
Mice
;
Mitosis
;
Phosphorylation
;
*Protein-Serine-Threonine Kinases
;
Proteins/metabolism
;
T-Lymphocytes/cytology
;
Telomere/*physiology
;
Telomeric Repeat Binding Protein 2
;
Tumor Cells, Cultured
;
Tumor Suppressor Protein p53/*metabolism
;
Tumor Suppressor Proteins
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
