55K isoform of CDK9 associates with Ku70 and is involved in DNA repair

Biochem Biophys Res Commun. 2010 Jun 25;397(2):245-50. doi: 10.1016/j.bbrc.2010.05.092. Epub 2010 May 20.


Positive elongation factor b (P-TEFb) is a cellular protein kinase that is required for RNA polymerase II (RNAP II) transcriptional elongation of protein coding genes. P-TEFb is a set of different molecular complexes, each containing CDK9 as the catalytic subunit. There are two isoforms of the CDK9 protein - the major 42KDa CDK9 isoform and the minor 55KDa isoform that is translated from an in-frame mRNA that arises from an upstream transcriptional start site. We found that shRNA depletion of the 55K CDK9 protein in HeLa cells induces apoptosis and double-strand DNA breaks (DSBs). The levels of apoptosis and DSBs induced by the depletion were reduced by expression of a 55K CDK9 protein variant resistant to the shRNA, indicating that these phenotypes are the consequence of depletion of the 55K protein and not off-target effects. We also found that the 55K CDK9 protein, but not the 42K CDK9 protein, specifically associates with Ku70, a protein involved in DSB repair. Our findings suggest that the 55K CDK9 protein may function in repair of DNA through an association with Ku70.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Nuclear / metabolism*
  • Cell Line
  • Cyclin-Dependent Kinase 9 / genetics
  • Cyclin-Dependent Kinase 9 / metabolism*
  • DNA Breaks, Double-Stranded*
  • DNA Repair*
  • DNA-Binding Proteins / metabolism*
  • Genetic Vectors
  • HeLa Cells
  • Humans
  • Ku Autoantigen
  • MicroRNAs / genetics
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism


  • Antigens, Nuclear
  • DNA-Binding Proteins
  • MicroRNAs
  • Protein Isoforms
  • Cyclin-Dependent Kinase 9
  • Xrcc6 protein, human
  • Ku Autoantigen