title: Functional human telomeres are recognized as DNA damage in G2 of the cell cycle.
abstract: Telomeres have to be distinguished from DNA breaks that initiate a DNA damage response. Proteins involved in the DNA damage response have previously been found at telomeres in transformed cells; however, the importance of these factors for telomere function has not been understood. Here, we show that telomeres of telomerase-negative primary cells recruit Mre11, phosphorylated NBS1, and ATM in every G2 phase of the cell cycle. This recruitment correlates with a partial release of telomeric POT1; moreover, telomeres were found to be accessible to modifying enzymes at this time in the cell cycle, suggesting that they are unprotected. Degradation of the MRN complex, as well as inhibition of ATM, led to telomere dysfunction. Consequentially, we propose that a localized DNA damage response at telomeres after replication is essential for recruiting the processing machinery that promotes formation of a chromosome end protection complex.
authors.affiliation: The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Ramiro E
authors.initials: RE
authors.lastname: Verdun
authors.forename: Laure
authors.initials: L
authors.lastname: Crabbe
authors.forename: Candy
authors.initials: C
authors.lastname: Haggblom
authors.forename: Jan
authors.initials: J
authors.lastname: Karlseder
mesh_terms: D002460:Cell Line; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016195:G2 Phase / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016615:Telomere / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins