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

Bauerschmidt, Christina, Arrichiello, Cecilia, Burdak-Rothkamm, Susanne, Woodcock, Michael, Hill, Mark A, Stevens, David L and Rothkamm, Kai (2010) Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin. NUCLEIC ACIDS RESEARCH, 38 (2). pp. 477-487.

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Hela Cells, Chromatin, Humans, Chromosome Aberrations, Cell Cycle Proteins, DNA-Binding Proteins, Tumor Suppressor Proteins, Nuclear Proteins, Chromosomal Proteins, Non-Histone, Phosphoproteins, Mitosis, G2 Phase, DNA Repair, DNA Replication, RNA Interference, Radiation Tolerance, DNA-Activated Protein Kinase, DNA Breaks, Double-Stranded, DNA Breaks, Single-Stranded, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Cohesins
Depositing User:	Symplectic Admin
Date Deposited:	10 Jul 2024 10:28
Last Modified:	10 Jul 2024 10:28
DOI:	10.1093/nar/gkp976
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3182749