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PMID:24095731
| Citation |
Ribes-Zamora, A, Indiviglio, SM, Mihalek, I, Williams, CL and Bertuch, AA (2013) TRF2 interaction with Ku heterotetramerization interface gives insight into c-NHEJ prevention at human telomeres. Cell Rep 5:194-206 |
|---|---|
| Abstract |
Telomeres are protected from nonhomologous end-joining (NHEJ) to avoid deleterious chromosome fusions, yet they associate with the Ku heterodimer that is principal in the classical NHEJ (c-NHEJ) pathway. T-loops have been proposed to inhibit Ku's association with telomeric ends, thus inhibiting c-NHEJ; however, deficiencies in the t-loop model suggest additional mechanisms are in effect. We demonstrate that TRF2 interacts with Ku at telomeres and via residues in Ku70 helix 5 (α5), which are vital for NHEJ. We show that Ku's interaction with a TRF2 mutant that induces telomeric fusions is significantly impaired. Additionally, we demonstrate that Ku70 α5 is required for Ku self-association in live cells, which can bridge DNA ends. Together, these findings lead us to propose a model in which telomeres are directly protected from c-NHEJ via TRF2 impeding Ku's ability to synapse telomere ends. |
| Links |
PubMed PMC3984498 Online version:10.1016/j.celrep.2013.08.040 |
| Keywords |
Antigens, Nuclear/chemistry; Antigens, Nuclear/genetics; Antigens, Nuclear/metabolism; DNA End-Joining Repair; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Humans; Ku Autoantigen; Models, Molecular; Protein Multimerization; Recombination, Genetic; Telomere/chemistry; Telomere/genetics; Telomere/metabolism; Telomeric Repeat Binding Protein 2/genetics; Telomeric Repeat Binding Protein 2/metabolism |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
HUMAN:XRCC6 |
part_of |
GO:0043564: Ku70:Ku80 complex |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
HUMAN:XRCC6 |
involved_in |
GO:0097680: double-strand break repair via classical nonhomologous end joining |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
HUMAN:XRCC6 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q13426 |
F |
Seeded From UniProt |
complete | |
|
HUMAN:XRCC6 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q9H9Q4 |
F |
Seeded From UniProt |
complete | |
|
HUMAN:XRCC6 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P54274 |
F |
Seeded From UniProt |
complete | |
|
HUMAN:XRCC6 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q15554 |
F |
|
Seeded From UniProt |
complete |
|
HUMAN:XRCC6 |
involved_in |
GO:0000723: telomere maintenance |
ECO:0000304: author statement supported by traceable reference used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
HUMAN:XRCC5 |
part_of |
GO:0043564: Ku70:Ku80 complex |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
HUMAN:XRCC5 |
involved_in |
GO:0032204: regulation of telomere maintenance |
ECO:0000304: author statement supported by traceable reference used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
HUMAN:TERF1 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P12956 |
F |
Seeded From UniProt |
complete | |
|
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P12956 |
F |
Seeded From UniProt |
complete | ||
|
enables |
GO:0044877: protein-containing complex binding |
ECO:0000353: physical interaction evidence used in manual assertion |
ComplexPortal:CPX-1993 |
F |
|
Seeded From UniProt |
complete | |
|
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P12956 |
F |
Seeded From UniProt |
complete | ||
|
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q9NYB0 |
F |
|
Seeded From UniProt |
complete | |
|
involved_in |
GO:0016233: telomere capping |
ECO:0000304: author statement supported by traceable reference used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P12956 |
F |
Seeded From UniProt |
complete | ||
|
HUMAN:TE2IP |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q15554 |
F |
|
Seeded From UniProt |
complete |
|
enables |
GO:0044877: protein-containing complex binding |
ECO:0000353: physical interaction evidence used in manual assertion |
ComplexPortal:CPX-1993 |
F |
occurs_at:(GO:0000781) |
Seeded From UniProt |
complete | |
|
involved_in |
GO:0031848: protection from non-homologous end joining at telomere |
ECO:0000353: physical interaction evidence used in manual assertion |
ComplexPortal:CPX-1993 |
P |
Seeded From UniProt |
complete | ||
Notes
See also
References
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