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Telomere dysfunction as a tool to identify novel DNA damage factors
Author(s) -
Bartocci Cristina,
Yates John,
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.933.7
Subject(s) - telomere , dna damage , chromatin , biology , dna , genomic dna , shelterin , dna repair , genetics , embryonic stem cell , microbiology and biotechnology , computational biology , gene , dna binding protein , transcription factor
The DNA damage response (DDR) pathway plays an essential tumor suppressive role ensuring the integrity of genomic information. Two major limitations have hindered the research in this field: i) the unpredictable location of DNA damage sites induced by conventional DNA damage‐inducing agents, ii) the lack of a technique for the isolation of proteins associated with a given DNA substrate. I have overcome these limitations by taking advantage of: i) telomere dysfunction as a tool to induce DNA damage to specific genomic loci, ii) a novel technique developed to isolate proteins associated with specific chromatin loci termed Proteomics of Isolated Chromatin segments (PICh). I performed the PICh purification on Terf2 F/F Rosa26‐Cre‐ER T2 mouse embryonic fibroblasts (MEFs), in which deletion of both alleles of Terf2 gives rise to a DDR at chromosome ends. The purification identified 95 proteins uniquely associated with dysfunctional telomeres, among which I selected a subset of candidates for confirmation of their localization to damaged telomeres and for their characterization as potential novel DDR factors. Research Support Source ADI