Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

Autophosphorylation of $DNA-PK_{CS}$ Regulates Its Dynamics at DNA Double-Strand Breaks

Naoya Uematsu, Eric Weterings, Ken-ichi Yano, Keiko Morotomi-Yano, Burkhard Jakob, Gisela Taucher-Scholz, Pierre-Olivier Mari, Dik C. van Gent, Benjamin P. C. Chen and David J. Chen
The Journal of Cell Biology
Vol. 177, No. 2 (Apr. 23, 2007), pp. 219-229
Stable URL: http://www.jstor.org/stable/30049940
Page Count: 11
  • More info
  • Cite this Item
Autophosphorylation of $DNA-PK_{CS}$ Regulates Its Dynamics at DNA Double-Strand Breaks
Preview not available

Abstract

The DNA-dependent protein kinase catalytic subunit ($DNA-PK_{CS}$) plays an important role during the repair of DNA double-strand breaks (DSBs). It is recruited to DNA ends in the early stages of the nonhomologous end-joining (NHEJ) process, which mediates DSB repair. To study $DNA-PK_{CS}$ recruitment in vivo, we used a laser system to introduce DSBs in a specified region of the cell nucleus. We show that $DNA-PK_{CS}$ accumulates at DSB sites in a Ku80-dependent manner, and that neither the kinase activity nor the phosphorylation status of $DNA-PK_{CS}$ influences its initial accumulation. However, impairment of both of these functions results in deficient DSB repair and the maintained presence of $DNA-PK_{CS}$ at unrepaired DSBs. The use of photobleaching techniques allowed us to determine that the kinase activity and phosphorylation status of $DNA-PK_{CS}$ influence the stability of its binding to DNA ends. We suggest a model in which $DNA-PK_{CS}$ phosphorylation/autophosphorylation facilitates NHEJ by destabilizing the interaction of $DNA-PK_{CS}$ with the DNA ends.

Page Thumbnails

  • Thumbnail: Page 
219
    219
  • Thumbnail: Page 
220
    220
  • Thumbnail: Page 
221
    221
  • Thumbnail: Page 
222
    222
  • Thumbnail: Page 
223
    223
  • Thumbnail: Page 
224
    224
  • Thumbnail: Page 
225
    225
  • Thumbnail: Page 
226
    226
  • Thumbnail: Page 
227
    227
  • Thumbnail: Page 
228
    228
  • Thumbnail: Page 
229
    229