Opening the DNA repair toolbox: localization of DNA double strand breaks to the nuclear periphery

Cell Cycle. 2010 Jan 1;9(1):43-9. doi: 10.4161/cc.9.1.10317. Epub 2010 Jan 13.

Abstract

Efficient repair of DNA double strand breaks is essential for cells to avoid increased mutation rates, genomic instability, and even cell death. Consequently, cells have evolved multiple mechanisms for rapidly repairing these DNA lesions, including error-free homologous recombination as well as error-prone pathways such as nonhomologous end joining. What happens to DSBs that are repaired inefficiently or not at all? Recently, several studies in budding yeast have shown that these more recalcitrant DSBs are localized to the nuclear periphery through interactions between the nuclear envelope protein, Mps3, and proteins associated with DSB chromatin. Why these DSBs are tethered to the nuclear periphery is still not clear, though the current view is that alternative repair pathways may be activated at the periphery in a final attempt to repair the lesion. In this Extra View, we discuss these recent reports, and we show that the Est1 component of the telomerase machinery plays an essential role in anchoring DSB chromatin to the nuclear envelope protein, Mps3.

MeSH terms

  • Chromatin / metabolism*
  • DNA Breaks, Double-Stranded*
  • DNA Repair / genetics
  • DNA Repair / physiology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Saccharomycetales / genetics
  • Saccharomycetales / metabolism
  • Telomerase / genetics
  • Telomerase / metabolism

Substances

  • Chromatin
  • Nuclear Proteins
  • Telomerase