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, Vol. 38, No. 2, 01.2010, p. 477-87.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

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@article{991918792591433c946fae3d0d563688,
title = "Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin",
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.",
keywords = "Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins/antagonists & inhibitors, Chromatin/radiation effects, Chromosomal Proteins, Non-Histone/antagonists & inhibitors, Chromosome Aberrations, DNA Breaks, Double-Stranded, DNA Breaks, Single-Stranded, DNA Repair, DNA Replication, DNA-Activated Protein Kinase/antagonists & inhibitors, DNA-Binding Proteins/antagonists & inhibitors, G2 Phase, HeLa Cells, Humans, Mitosis, Nuclear Proteins/antagonists & inhibitors, Phosphoproteins/antagonists & inhibitors, Protein-Serine-Threonine Kinases/antagonists & inhibitors, RNA Interference, Radiation Tolerance, Tumor Suppressor Proteins/antagonists & inhibitors",
author = "Christina Bauerschmidt and Cecilia Arrichiello and Susanne Burdak-Rothkamm and Michael Woodcock and Hill, {Mark A} and Stevens, {David L} and Kai Rothkamm",
year = "2010",
month = jan,
doi = "10.1093/nar/gkp976",
language = "English",
volume = "38",
pages = "477--87",
journal = "NUCLEIC ACIDS RES",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "2",

}

RIS

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 -