RAD51 foci formation in response to DNA damage is modulated by TIP49

Int J Biochem Cell Biol. 2009 Apr;41(4):925-33. doi: 10.1016/j.biocel.2008.09.004. Epub 2008 Sep 13.

Abstract

Chromatin modification plays an important role in modulating the access of homologous recombination proteins to the sites of DNA damage. TIP49 is highly conserved component of chromatin modification/remodeling complexes, but its involvement in homologous recombination repair in mammalian cells has not been examined in details. In the present communication we studied the role of TIP49 in recruitment of the key homologous recombination protein RAD51 to sites of DNA damage. RAD51 redistribution to chromatin and nuclear foci formation induced by double-strand breaks and interstrand crosslinks were followed under conditions of TIP49 depletion by RNA interference. TIP49 silencing reduced RAD51 recruitment to chromatin and nuclear foci formation to about 50% of that of the control. Silencing of TIP48, which is closely related to TIP49, induced a similar reduction in RAD51 foci formation. RAD51 foci reduction in TIP49-silenced cells was not a result of defective DNA damage checkpoint signaling as judged by the normal histone H2AX phosphorylation and cell cycle distribution. Treatment with the histone deacetylase inhibitor sodium butyrate restored RAD51 foci formation in the TIP49-depleted cells. The results suggest that as a constituent of chromatin modification complexes TIP49 may facilitate the access of the repair machinery to the sites of DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle
  • Cell Line, Tumor
  • DNA Damage*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Repair
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • Phosphorylation
  • RNA Interference
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism*

Substances

  • Carrier Proteins
  • Rad51 Recombinase
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • RUVBL1 protein, human