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PMID:15657433

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Citation

Yang, Q, Zheng, YL and Harris, CC (2005) POT1 and TRF2 cooperate to maintain telomeric integrity. Mol. Cell. Biol. 25:1070-80

Abstract

Mammalian telomeric DNA contains duplex TTAGGG repeats and single-stranded overhangs. POT1 (protection of telomeres 1) is a telomere-specific single-stranded DNA-binding protein, highly conserved in eukaryotes. The biological function of human POT1 is not well understood. In the present study, we demonstrate that POT1 plays a key role in telomeric end protection. The reduction of POT1 by RNA interference led to the loss of telomeric single-stranded overhangs and induced apoptosis, chromosomal instability, and senescence in cells. POT1 and TRF2 interacted with each other to form a complex with telomeric DNA. A dominant negative TRF2, TRF2(DeltaBDeltaM), bound to POT1 and prevented it from binding to telomeres. POT1 overexpression protected against TRF2(DeltaBDeltaM)-induced loss of telomeric single-stranded overhangs, chromosomal instability, and senescence. These results demonstrate that POT1 and TRF2 share in part in the same pathway for telomere capping and suggest that POT1 binds to the telomeric single-stranded DNA in the D-loop and cooperates with TRF2 in t-loop maintenance.

Links

PubMed PMC544002 Online version:10.1128/MCB.25.3.1070-1080.2005

Keywords

Apoptosis/physiology; Cell Aging/physiology; Chromosomal Instability/physiology; Fibroblasts/metabolism; Humans; In Situ Hybridization, Fluorescence; Protein Binding; RNA, Small Interfering/metabolism; Telomere/metabolism; Telomere-Binding Proteins/metabolism; Telomeric Repeat Binding Protein 2/metabolism; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TERF2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NUX5

F

Seeded From UniProt

complete

HUMAN:POTE1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15554

F

Seeded From UniProt

complete

HUMAN:TERF2

involved_in

GO:0016233: telomere capping

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TERF2

involved_in

GO:0032211: negative regulation of telomere maintenance via telomerase

ECO:0000305: curator inference used in manual assertion

GO:0016233

P

Seeded From UniProt

complete

HUMAN:POTE1

involved_in

GO:0016233: telomere capping

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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