Transcriptional elongation requires DNA break-induced signalling

Heeyoun Bunch, Brian P. Lawney, Yu Fen Lin, Aroumougame Asaithamby, Ayesha Murshid, Yaoyu E. Wang, Benjamin P C Chen, Stuart K. Calderwood

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

We have previously shown that RNA polymerase II (Pol II) pause release and transcriptional elongation involve phosphorylation of the factor TRIM28 by the DNA damage response (DDR) kinases ATM and DNA-PK. Here we report a significant role for DNA breaks and DDR signalling in the mechanisms of transcriptional elongation in stimulus-inducible genes in humans. Our data show the enrichment of TRIM28 and γH2AX on serum-induced genes and the important function of DNA-PK for Pol II pause release and transcriptional activation-coupled DDR signalling on these genes. γH2AX accumulation decreases when P-TEFb is inhibited, confirming that DDR signalling results from transcriptional elongation. In addition, transcriptional elongation-coupled DDR signalling involves topoisomerase II because inhibiting this enzyme interferes with Pol II pause release and γH2AX accumulation. Our findings propose that DDR signalling is required for effective Pol II pause release and transcriptional elongation through a novel mechanism involving TRIM28, DNA-PK and topoisomerase II.

Original languageEnglish (US)
Article number10191
JournalNature Communications
Volume6
DOIs
StatePublished - Dec 16 2015

Fingerprint

DNA Breaks
DNA Damage
elongation
Elongation
deoxyribonucleic acid
DNA
Type II DNA Topoisomerase
damage
genes
Positive Transcriptional Elongation Factor B
DNA Polymerase II
Polynucleotide 5'-Hydroxyl-Kinase
Genes
RNA Polymerase II
Transcriptional Activation
asynchronous transfer mode
phosphorylation
Phosphorylation
Automatic teller machines
serums

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Bunch, H., Lawney, B. P., Lin, Y. F., Asaithamby, A., Murshid, A., Wang, Y. E., ... Calderwood, S. K. (2015). Transcriptional elongation requires DNA break-induced signalling. Nature Communications, 6, [10191]. https://doi.org/10.1038/ncomms10191

Transcriptional elongation requires DNA break-induced signalling. / Bunch, Heeyoun; Lawney, Brian P.; Lin, Yu Fen; Asaithamby, Aroumougame; Murshid, Ayesha; Wang, Yaoyu E.; Chen, Benjamin P C; Calderwood, Stuart K.

In: Nature Communications, Vol. 6, 10191, 16.12.2015.

Research output: Contribution to journalArticle

Bunch, Heeyoun ; Lawney, Brian P. ; Lin, Yu Fen ; Asaithamby, Aroumougame ; Murshid, Ayesha ; Wang, Yaoyu E. ; Chen, Benjamin P C ; Calderwood, Stuart K. / Transcriptional elongation requires DNA break-induced signalling. In: Nature Communications. 2015 ; Vol. 6.
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