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Transcriptional Elongation Requires DNA Double Stand Break and Repair
Author(s) -
Bunch Heeyoun,
Lawney Brian,
Asaithamby Aroumougame,
Murshid Ayesha,
Wang Yaoyu,
Chen Benjamin,
Calderwood Stuart
Publication year - 2015
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.29.1_supplement.877.1
Subject(s) - elongation , dna , computational biology , microbiology and biotechnology , chemistry , biology , genetics , materials science , ultimate tensile strength , metallurgy
TRIM28 plays a key role in transcriptional regulation by controlling RNA polymerase II entry from promoter‐proximal pausing into processive elongation. We have shown that transcriptional activation involves TRIM28 phosphorylation by members of the phosphatidylinositol 3‐kinase‐related kinases (PIKKs) such as DNA‐PK and ATM at HSPA1B . Here, we show that DNA double strand break (DSB) and repair proteins such as Topoisomerase IIB, phosphorylated TRIM28 (S824), phosphorylated DNA‐PK (T2609), Ku70, and gH2AX, were rapidly accumulated at activated paused genes in vivo . Transcriptional activation‐induced DSB was indicated by enrichment of γH2AX and activated DNA repair enzymes through in vivo cell based and genome‐wide analyses and visualized through in vitro biochemical analysis. Our data reveal a novel transcriptional activation mechanism involving rapid DSB and repair.