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Blocking ubiquitin deposition at telomeres: the molecular mechanism of TRF2‐mediated end protection
Author(s) -
Okamoto Keiji,
Denchi Eros Lazzerini
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.935.1
Subject(s) - telomere , dna damage , histone , chromosome , microbiology and biotechnology , dna repair , biology , dna , genetics , gene
“End protection” defines that ability of telomeres to cap and protect chromosome ends from the DNA damage response machinery. When end protection is lost, chromosome ends are recognized as sites of DNA lesion and are repaired by the DNA repair machinery resulting in end‐to‐end chromosome fusions, an unstable genomic configuration. The telomere repeat binding factor TRF2 plays a crucial role in this process as shown by the fact that its depletion is sufficient to trigger activation of DNA damage response at chromosome ends. In order to uncover the molecular mechanism employed by TRF2 to protect chromosome ends we performed a screen to identify the critical region within TRF2 involved in end protection. Our data show that a critical mechanism for TRF2‐mediated suppression of DNA damage activation involves suppression of RNF168‐dependent ubiquitination of histone H2A(X). Prevention of this histone modification is both required and sufficient to suppress activation of DNA damage response at chromosome ends. Furthermore, our data reveal a critical role for de‐ubiquitinase enzymes for telomere integrity. ADI