DNA damage-activated ABL-MyoD signaling contributes to DNA repair in skeletal myoblasts

M. Simonatto, F. Marullo, F. Chiacchiera, A. Musaró, J. Y J Wang, L. Latella, P. L. Puri

Research output: Contribution to journalArticlepeer-review

Abstract

Previous works have established a unique function of MyoD in the control of muscle gene expression during DNA damage response in myoblasts. Phosphorylation by DNA damage-activated ABL tyrosine kinase transiently inhibits MyoD-dependent activation of transcription in response to genotoxic stress. We show here that ABL-MyoD signaling is also an essential component of the DNA repair machinery in myoblasts exposed to genotoxic stress. DNA damage promoted the recruitment of MyoD to phosphorylated Nbs1 (pNbs1)-containing repair foci, and this effect was abrogated by either ABL knockdown or the ABL kinase inhibitor imatinib. Upon DNA damage, MyoD and pNbs1 were detected on the chromatin to MyoD target genes without activating transcription. DNA damage-mediated tyrosine phosphorylation was required for MyoD recruitment to target genes, as the ABL phosphorylation-resistant MyoD mutant (MyoD Y30F) failed to bind the chromatin following DNA damage, while retaining the ability to activate transcription in response to differentiation signals. Moreover, MyoD Y30F exhibited an impaired ability to promote repair in a heterologous system, as compared with MyoD wild type (WT). Consistently, MyoD-null satellite cells (SCs) displayed impaired DNA repair that was rescued by reintroduction of MyoD WT but not by MyoD Y30F. In addition, inhibition of ABL kinase prevented MyoD WT-mediated rescue of DNA repair in MyoD-null SCs. These results identify an unprecedented contribution of MyoD to DNA repair and suggest that ABL-MyoD signaling coordinates DNA repair and transcription in myoblasts.

Original languageEnglish
Pages (from-to)1664-1674
Number of pages11
JournalCell Death and Differentiation
Volume20
Issue number12
DOIs
Publication statusPublished - Dec 2013

Keywords

  • ABL
  • chromatin
  • DNA damage
  • DNA repair
  • MyoD

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Fingerprint

Dive into the research topics of 'DNA damage-activated ABL-MyoD signaling contributes to DNA repair in skeletal myoblasts'. Together they form a unique fingerprint.

Cite this