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PMID:17694070

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Citation

Wu, Y, Xiao, S and Zhu, XD (2007) MRE11-RAD50-NBS1 and ATM function as co-mediators of TRF1 in telomere length control. Nat. Struct. Mol. Biol. 14:832-40

Abstract

Human telomeres are associated with ATM and the protein complex consisting of MRE11, RAD50 and NBS1 (MRN), which are central to maintaining genomic stability. Here we show that when targeted to telomeres, wild-type RAD50 downregulates telomeric association of TRF1, a negative regulator of telomere maintenance. TRF1 binding to telomeres is upregulated in cells deficient in NBS1 or under ATM inhibition. The TRF1 association with telomeres induced by ATM inhibition is abrogated in cells lacking MRE11 or NBS1, suggesting that MRN and ATM function in the same pathway controlling TRF1 binding to telomeres. The ability of TRF1 to interact with telomeric DNA in vitro is impaired by ATM-mediated phosphorylation. We propose that MRN is required for TRF1 phosphorylation by ATM and that such phosphorylation results in the release of TRF1 from telomeres, promoting telomerase access to the ends of telomeres.

Links

PubMed Online version:10.1038/nsmb1286

Keywords

Ataxia Telangiectasia Mutated Proteins; Cell Cycle Proteins/physiology; Cell Line; DNA Repair Enzymes/physiology; DNA-Binding Proteins/physiology; Humans; MRE11 Homologue Protein; Nuclear Proteins/physiology; Phosphorylation; Protein Binding; Protein-Serine-Threonine Kinases/physiology; Telomere; Telomeric Repeat Binding Protein 1/physiology; Tumor Suppressor Proteins/physiology

Significance

Annotations

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

HUMAN:NBN

involved_in

GO:1904354: negative regulation of telomere capping

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P54274)

Seeded From UniProt

complete

HUMAN:TERF1

enables

GO:0098505: G-rich strand telomeric DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ATM

involved_in

GO:1904354: negative regulation of telomere capping

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P54274)

Seeded From UniProt

complete

HUMAN:RAD50

involved_in

GO:1904354: negative regulation of telomere capping

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P54274)

Seeded From UniProt

complete

HUMAN:TE2IP

enables

GO:0098505: G-rich strand telomeric DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ATM

involved_in

GO:0006468: protein phosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ATM

involved_in

GO:1904358: positive regulation of telomere maintenance via telomere lengthening

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ATM

involved_in

GO:1904354: negative regulation of telomere capping

ECO:0000315: mutant phenotype evidence used in manual assertion

P

has_regulation_target:(UniProtKB:P54274)

Seeded From UniProt

complete

HUMAN:TERF2

enables

GO:0098505: G-rich strand telomeric DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

Notes

See also

References

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