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Mol Cell Biol. 2003 Sep;23(18):6533-41.

Targeted deletion reveals an essential function for the telomere length regulator Trf1.

Author information

1
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA.

Abstract

The human telomeric DNA binding factor TRF1 (hTRF1) and its interacting proteins TIN2, tankyrase 1 and 2, and PINX1 have been implicated in the regulation of telomerase-dependent telomere length maintenance. Here we show that targeted deletion of exon 1 of the mouse gene encoding Trf1 causes early (day 5 to 6 postcoitus) embryonic lethality. The absence of telomerase did not alter the Terf1(ex1Delta/ex1Delta) lethality, indicating that the phenotype was not due to inappropriate telomere elongation by telomerase. Terf1(ex1Delta/ex1Delta) blastocysts had a severe growth defect of the inner cell mass that was accompanied by apoptosis. However, no evidence was found for telomere uncapping causing this cell death; chromosome spreads of Terf1(ex1Delta/ex1Delta) blastocysts did not reveal chromosome end-to-end fusions, and p53 deficiency only briefly delayed Terf1(ex1Delta/ex1Delta) lethality. These data suggest that murine Trf1 has an essential function that is independent of telomere length regulation.

PMID:
12944479
PMCID:
PMC193696
DOI:
10.1128/mcb.23.18.6533-6541.2003
[Indexed for MEDLINE]
Free PMC Article

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