title: Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres.
abstract: Telomeres allow cells to distinguish natural chromosome ends from damaged DNA and protect the ends from degradation and fusion. In human cells, telomere protection depends on the TTAGGG repeat binding factor, TRF2 (refs 1-4), which has been proposed to remodel telomeres into large duplex loops (t-loops). Here we show by nanoelectrospray tandem mass spectrometry that RAD50 protein is present in TRF2 immunocomplexes. Protein blotting showed that a small fraction of RAD50, MRE11 and the third component of the MRE11 double-strand break (DSB) repair complex, the Nijmegen breakage syndrome protein (NBS1), is associated with TRF2. Indirect immunofluorescence demonstrated the presence of RAD50 and MRE11 at interphase telomeres. NBS1 was associated with TRF2 and telomeres in S phase, but not in G1 or G2. Although the MRE11 complex accumulated in irradiation-induced foci (IRIFs) in response to gamma-irradiation, TRF2 did not relocate to IRIFs and irradiation did not affect the association of TRF2 with the MRE11 complex, arguing against a role for TRF2 in DSB repair. Instead, we propose that the MRE11 complex functions at telomeres, possibly by modulating t-loop formation.
authors.affiliation: The Rockefeller University, New York, New York, USA.
authors.forename: X D
authors.initials: XD
authors.lastname: Zhu
authors.forename: B
authors.initials: B
authors.lastname: Küster
authors.forename: M
authors.initials: M
authors.lastname: Mann
authors.forename: J H
authors.initials: JH
authors.lastname: Petrini
authors.forename: T
authors.initials: T
authors.lastname: de Lange
mesh_terms: D017766:Acid Anhydride Hydrolases; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D035341:Telomeric Repeat Binding Protein 2; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes