Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription

Nucleic Acids Res. 2014 Jul;42(13):8473-85. doi: 10.1093/nar/gku565. Epub 2014 Jul 2.

Abstract

Chromatin compaction of deoxyribonucleic acid (DNA) presents a major challenge to the detection and removal of DNA damage. Helix-distorting DNA lesions that block transcription are specifically repaired by transcription-coupled nucleotide excision repair, which is initiated by binding of the CSB protein to lesion-stalled RNA polymerase II. Using live cell imaging, we identify a novel function for two distinct mammalian ISWI adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in resolving lesion-stalled transcription. Human ISWI isoform SMARCA5/SNF2H and its binding partners ACF1 and WSTF are rapidly recruited to UV-C induced DNA damage to specifically facilitate CSB binding and to promote transcription recovery. SMARCA5 targeting to UV-C damage depends on transcription and histone modifications and requires functional SWI2/SNF2-ATPase and SLIDE domains. After initial recruitment to UV damage, SMARCA5 re-localizes away from the center of DNA damage, requiring its HAND domain. Our studies support a model in which SMARCA5 targeting to DNA damage-stalled transcription sites is controlled by an ATP-hydrolysis-dependent scanning and proofreading mechanism, highlighting how SWI2/SNF2 chromatin remodelers identify and bind nucleosomes containing damaged DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / analysis
  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism*
  • Cell Line
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone / analysis
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Damage
  • DNA Helicases / metabolism
  • DNA Repair Enzymes / metabolism
  • DNA Repair*
  • Histones / metabolism
  • Humans
  • Poly-ADP-Ribose Binding Proteins
  • Protein Structure, Tertiary
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Ultraviolet Rays

Substances

  • BAZ1A protein, human
  • BAZ1B protein, human
  • Chromosomal Proteins, Non-Histone
  • Histones
  • Poly-ADP-Ribose Binding Proteins
  • Transcription Factors
  • Adenosine Triphosphatases
  • SMARCA5 protein, human
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes