PMID- 10037601
OWN - NLM
STAT- MEDLINE
DCOM- 19990312
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 283
IP  - 5406
DP  - 1999 Feb 26
TI  - p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2.
PG  - 1321-5
AB  - 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.
FAU - Karlseder, J
AU  - Karlseder J
AD  - Laboratory for Cell Biology and Genetics, The Rockefeller University, New York,
      NY 10021, USA. Cell Genesys, Foster City, CA 94405, USA.
FAU - Broccoli, D
AU  - Broccoli D
FAU - Dai, Y
AU  - Dai Y
FAU - Hardy, S
AU  - Hardy S
FAU - de Lange, T
AU  - de Lange T
LA  - eng
GR  - GM49046/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proteins)
RN  - 0 (Telomeric Repeat Binding Protein 2)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (Atm protein, mouse)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
SB  - IM
MH  - Adenoviridae/genetics/physiology
MH  - Animals
MH  - *Apoptosis
MH  - Ataxia Telangiectasia/pathology
MH  - Ataxia Telangiectasia Mutated Proteins
MH  - B-Lymphocytes/cytology
MH  - Cell Cycle Proteins
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cloning, Molecular
MH  - DNA Damage
MH  - DNA-Binding Proteins/chemistry/genetics/*physiology
MH  - Genetic Vectors
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Mice
MH  - Mitosis
MH  - Phosphorylation
MH  - *Protein-Serine-Threonine Kinases
MH  - Proteins/metabolism
MH  - T-Lymphocytes/cytology
MH  - Telomere/*physiology
MH  - Telomeric Repeat Binding Protein 2
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Tumor Suppressor Proteins
EDAT- 1999/02/26 00:00
MHDA- 1999/02/26 00:01
CRDT- 1999/02/26 00:00
PHST- 1999/02/26 00:00 [pubmed]
PHST- 1999/02/26 00:01 [medline]
PHST- 1999/02/26 00:00 [entrez]
AID - 10.1126/science.283.5406.1321 [doi]
PST - ppublish
SO  - Science. 1999 Feb 26;283(5406):1321-5. doi: 10.1126/science.283.5406.1321.