Functional human telomeres are recognized as DNA damage in G2 of the cell cycle

Ramiro E. Verdun, Laure Crabbe, Candy Haggblom, Jan Karlseder

Research output: Contribution to journalArticle

219 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)551-561
Number of pages11
JournalMolecular Cell
Volume20
Issue number4
DOIs
StatePublished - Nov 23 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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