Super-resolution imaging identifies PARP1 and the Ku complex acting as DNA double-strand break sensors

Nucleic Acids Res. 2018 Apr 20;46(7):3446-3457. doi: 10.1093/nar/gky088.


DNA double-strand breaks (DSBs) are fatal DNA lesions and activate a rapid DNA damage response. However, the earliest stage of DSB sensing remains elusive. Here, we report that PARP1 and the Ku70/80 complex localize to DNA lesions considerably earlier than other DSB sensors. Using super-resolved fluorescent particle tracking, we further examine the relocation kinetics of PARP1 and the Ku70/80 complex to a single DSB, and find that PARP1 and the Ku70/80 complex are recruited to the DSB almost at the same time. Notably, only the Ku70/80 complex occupies the DSB exclusively in the G1 phase; whereas PARP1 competes with the Ku70/80 complex at the DSB in the S/G2 phase. Moreover, in the S/G2 phase, PARP1 removes the Ku70/80 complex through its enzymatic activity, which is further confirmed by in vitro DSB-binding assays. Taken together, our results reveal PARP1 and the Ku70/80 complex as critical DSB sensors, and suggest that PARP1 may function as an important regulator of the Ku70/80 complex at the DSBs in the S/G2 phase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Nucleus / genetics
  • DNA Breaks, Double-Stranded*
  • DNA Damage / genetics
  • DNA End-Joining Repair / genetics
  • DNA Repair / genetics
  • Genome
  • Kinetics
  • Ku Autoantigen / chemistry
  • Ku Autoantigen / genetics*
  • Mice
  • NIH 3T3 Cells
  • Optical Imaging / methods*
  • Poly (ADP-Ribose) Polymerase-1 / chemistry
  • Poly (ADP-Ribose) Polymerase-1 / genetics*


  • Parp1 protein, mouse
  • Poly (ADP-Ribose) Polymerase-1
  • Ku Autoantigen