Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin
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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; Rothkamm, Kai.
in: NUCLEIC ACIDS RES, Jahrgang 38, Nr. 2, 01.2010, S. 477-87.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin
AU - Bauerschmidt, Christina
AU - Arrichiello, Cecilia
AU - Burdak-Rothkamm, Susanne
AU - Woodcock, Michael
AU - Hill, Mark A
AU - Stevens, David L
AU - Rothkamm, Kai
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - Ataxia Telangiectasia Mutated Proteins
KW - Cell Cycle Proteins/antagonists & inhibitors
KW - Chromatin/radiation effects
KW - Chromosomal Proteins, Non-Histone/antagonists & inhibitors
KW - Chromosome Aberrations
KW - DNA Breaks, Double-Stranded
KW - DNA Breaks, Single-Stranded
KW - DNA Repair
KW - DNA Replication
KW - DNA-Activated Protein Kinase/antagonists & inhibitors
KW - DNA-Binding Proteins/antagonists & inhibitors
KW - G2 Phase
KW - HeLa Cells
KW - Humans
KW - Mitosis
KW - Nuclear Proteins/antagonists & inhibitors
KW - Phosphoproteins/antagonists & inhibitors
KW - Protein-Serine-Threonine Kinases/antagonists & inhibitors
KW - RNA Interference
KW - Radiation Tolerance
KW - Tumor Suppressor Proteins/antagonists & inhibitors
U2 - 10.1093/nar/gkp976
DO - 10.1093/nar/gkp976
M3 - SCORING: Journal article
C2 - 19906707
VL - 38
SP - 477
EP - 487
JO - NUCLEIC ACIDS RES
JF - NUCLEIC ACIDS RES
SN - 0305-1048
IS - 2
ER -