Double-strand DNA breaks recruit the centromeric histone CENP-A
Double-strand DNA breaks recruit the centromeric histone CENP-A
The histone H3 variant CENP-A is required for epigenetic specification of centromere identity through a loading mechanism independent of DNA sequence. Using multiphoton absorption and DNA cleavage at unique sites by I- Sce I endonuclease, we demonstrate that CENP-A is rapidly recruited to double-strand breaks in DNA, along with three components (CENP-N, CENP-T, and CENP-U) associated with CENP-A at centromeres. The centromere-targeting domain of CENP-A is both necessary and sufficient for recruitment to double-strand breaks. CENP-A accumulation at DNA breaks is enhanced by active non-homologous end-joining but does not require DNA-PKcs or Ligase IV, and is independent of H2AX. Thus, induction of a double-strand break is sufficient to recruit CENP-A in human and mouse cells. Finally, since cell survival after radiation-induced DNA damage correlates with CENP-A expression level, we propose that CENP-A may have a function in DNA repair.
- University of California, San Diego United States
- National Cancer Institute United States
- Ludwig Cancer Research United States
- University of California, San Francisco United States
- Scripps Research Institute United States
Protein Structure, DNA Repair, Active, Chromosomal Proteins, Non-Histone, Recombinant Fusion Proteins, Centromere, Green Fluorescent Proteins, DNA repair, Biological Transport, Active, Autoantigens, Models, Biological, Cell Line, Histones, Double-Stranded, Mice, Models, Genetics, Animals, Humans, DNA Breaks, Double-Stranded, Deoxyribonucleases, Type II Site-Specific, Cancer, Deoxyribonucleases, DNA Breaks, Biological Transport, Non-Histone, Type II Site-Specific, Biological, Protein Structure, Tertiary, Chromosomal Proteins, Kinetics, chromatin, Generic health relevance, Tertiary, Centromere Protein A, DNA Damage
Protein Structure, DNA Repair, Active, Chromosomal Proteins, Non-Histone, Recombinant Fusion Proteins, Centromere, Green Fluorescent Proteins, DNA repair, Biological Transport, Active, Autoantigens, Models, Biological, Cell Line, Histones, Double-Stranded, Mice, Models, Genetics, Animals, Humans, DNA Breaks, Double-Stranded, Deoxyribonucleases, Type II Site-Specific, Cancer, Deoxyribonucleases, DNA Breaks, Biological Transport, Non-Histone, Type II Site-Specific, Biological, Protein Structure, Tertiary, Chromosomal Proteins, Kinetics, chromatin, Generic health relevance, Tertiary, Centromere Protein A, DNA Damage
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