Back to Search
Start Over
Telomere protection by TPP1/POT1 requires tethering to TIN2.
- Source :
-
Molecular cell [Mol Cell] 2011 Nov 18; Vol. 44 (4), pp. 647-59. - Publication Year :
- 2011
-
Abstract
- To prevent ATR activation, telomeres deploy the single-stranded DNA binding activity of TPP1/POT1a. POT1a blocks the binding of RPA to telomeres, suggesting that ATR is repressed through RPA exclusion. However, comparison of the DNA binding affinities and abundance of TPP1/POT1a and RPA indicates that TPP1/POT1a by itself is unlikely to exclude RPA. We therefore analyzed the central shelterin protein TIN2, which links TPP1/POT1a (and POT1b) to TRF1 and TRF2 on the double-stranded telomeric DNA. Upon TIN2 deletion, telomeres lost TPP1/POT1a, accumulated RPA, elicited an ATR signal, and showed all other phenotypes of POT1a/b deletion. TIN2 also affected the TRF2-dependent repression of ATM kinase signaling but not to TRF2-mediated inhibition of telomere fusions. Thus, while TIN2 has a minor contribution to the repression of ATM by TRF2, its major role is to stabilize TPP1/POT1a on the ss telomeric DNA, thereby allowing effective exclusion of RPA and repression of ATR signaling.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Ataxia Telangiectasia Mutated Proteins
Cell Cycle Proteins genetics
Cell Cycle Proteins metabolism
DNA Damage
DNA, Single-Stranded chemistry
DNA, Single-Stranded genetics
DNA-Binding Proteins genetics
HeLa Cells
Humans
Mice
Mice, Knockout
Protein Binding genetics
Recombinant Proteins genetics
Recombinant Proteins metabolism
Shelterin Complex
Telomere-Binding Proteins genetics
Telomeric Repeat Binding Protein 2 genetics
Telomeric Repeat Binding Protein 2 metabolism
DNA Repair
DNA, Single-Stranded metabolism
DNA-Binding Proteins metabolism
Gene Expression
Signal Transduction genetics
Telomere metabolism
Telomere-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 44
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 22099311
- Full Text :
- https://doi.org/10.1016/j.molcel.2011.08.043