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BMI1 is recruited to DNA breaks and contributes to DNA damage-induced H2A ubiquitination and repair.

DNA damage activates signaling pathways that lead to modification of local chromatin and recruitment of DNA repair proteins. Multiple DNA repair proteins having ubiquitin ligase activity are recruited to sites of DNA damage, where they ubiquitinate histones and other substrates. This DNA damage-induced histone ubiquitination is thought to play a critical role in mediating the DNA damage response. We now report that the polycomb protein BMI1 is rapidly recruited to sites of DNA damage, where it persists for more than 8 h. The sustained localization of BMI1 to damage sites is dependent on intact ATM and ATR and requires H2AX phosphorylation and recruitment of RNF8. BMI1 is required for DNA damage-induced ubiquitination of histone H2A at lysine 119. Loss of BMI1 leads to impaired repair of DNA double-strand breaks by homologous recombination and the accumulation of cells in G(2)/M. These data support a crucial role for BMI1 in the cellular response to DNA damage.

Pubmed ID: 21383063

Authors

  • Ginjala V
  • Nacerddine K
  • Kulkarni A
  • Oza J
  • Hill SJ
  • Yao M
  • Citterio E
  • van Lohuizen M
  • Ganesan S

Journal

Molecular and cellular biology

Publication Data

May 28, 2011

Associated Grants

None

Mesh Terms

  • Ataxia Telangiectasia Mutated Proteins
  • Blotting, Western
  • Cell Cycle
  • Cell Cycle Proteins
  • Chromatin Immunoprecipitation
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • DNA-Binding Proteins
  • Fluorescent Antibody Technique
  • HeLa Cells
  • Histones
  • Humans
  • Nuclear Proteins
  • Phosphorylation
  • Polycomb Repressive Complex 1
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Repressor Proteins
  • Signal Transduction
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases
  • Ubiquitination