Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin.

The cohesin protein complex holds sister chromatids together after synthesis until mitosis. It also contributes to post-replicative DNA repair in yeast and higher eukaryotes and accumulates at sites of laser-induced damage in human cells. Our goal was to determine whether the cohesin subunits SMC1 and Rad21 contribute to DNA double-strand ...
break repair in X-irradiated human cells in the G2 phase of the cell cycle. RNA interference-mediated depletion of SMC1 sensitized HeLa cells to X-rays. Repair of radiation-induced DNA double-strand breaks, measured by gammaH2AX/53BP1 foci analysis, was slower in SMC1- or Rad21-depleted cells than in controls in G2 but not in G1. Inhibition of the DNA damage kinase DNA-PK, but not ATM, further inhibited foci loss in cohesin-depleted cells in G2. SMC1 depletion had no effect on DNA single-strand break repair in either G1 or late S/G2. Rad21 and SMC1 were recruited to sites of X-ray-induced DNA damage in G2-phase cells, but not in G1, and only when DNA damage was concentrated in subnuclear stripes, generated by partially shielded ultrasoft X-rays. Our results suggest that the cohesin complex contributes to cell survival by promoting the repair of radiation-induced DNA double-strand breaks in G2-phase cells in an ATM-dependent pathway.
Mesh Terms:
Cell Cycle Proteins, Chromatin, Chromosomal Proteins, Non-Histone, Chromosome Aberrations, DNA Breaks, Double-Stranded, DNA Breaks, Single-Stranded, DNA Repair, DNA Replication, DNA-Activated Protein Kinase, DNA-Binding Proteins, G2 Phase, Hela Cells, Humans, Mitosis, Nuclear Proteins, Phosphoproteins, Protein-Serine-Threonine Kinases, RNA Interference, Radiation Tolerance, Tumor Suppressor Proteins
Nucleic Acids Res.
Date: Jan. 01, 2010
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