TIN2 Mediates Functions of TRF2 at Human Telomeres

Telomeres are protective structures at chromosome ends and are crucial for genomic stability. Mammalian TRF1 and TRF2 bind the double-stranded telomeric repeat sequence and in turn are bound by TIN2, TANK1, TANK2, and hRAP1. TRF1 is a negative regulator of telomere length in telomerase-positive cell...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2004-10, Vol.279 (42), p.43799-43804
Main Authors: Kim, Sahn-ho, Beausejour, Christian, Davalos, Albert R, Kaminker, Patrick, Heo, Seok-Jin, Campisi, Judith
Format: Article
Language:English
Subjects:
BASIC BIOLOGICAL SCIENCES
BIOLOGICAL FUNCTIONS
Cell Line
HUMAN POPULATIONS
Humans
Protein Binding
Recombinant Proteins - isolation & purification
Recombinant Proteins - metabolism
Telomerase - metabolism
Telomere - physiology
Telomere-Binding Proteins - isolation & purification
Telomere-Binding Proteins - metabolism
TELOMERES
Telomeric Repeat Binding Protein 1 - metabolism
Telomeric Repeat Binding Protein 2 - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Telomeres are protective structures at chromosome ends and are crucial for genomic stability. Mammalian TRF1 and TRF2 bind the double-stranded telomeric repeat sequence and in turn are bound by TIN2, TANK1, TANK2, and hRAP1. TRF1 is a negative regulator of telomere length in telomerase-positive cells, whereas TRF2 is important for telomere capping. TIN2 was identified as a TRF1-interacting protein that mediates TRF1 function. We show here that TIN2 also interacts with TRF2 in vitro and in yeast and mammalian cells. TIN2 mutants defective in binding of TRF1 or TRF2 induce a DNA damage response and destabilize TRF1 and TRF2 at telomeres in human cells. Our findings suggest that the functions of TRF1 and TRF2 are linked by TIN2.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M408650200