Cohesin phosphorylation and mobility of SMC1 at ionizing radiation-induced DNA double-strand breaks in human cells

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Cohesin phosphorylation and mobility of SMC1 at ionizing radiation-induced DNA double-strand breaks in human cells. / Bauerschmidt, Christina; Woodcock, Michael; Stevens, David L; Hill, Mark A; Rothkamm, Kai; Helleday, Thomas.

In: EXP CELL RES, Vol. 317, No. 3, 01.02.2011, p. 330-7.

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

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@article{3bdec25482cb4995afcbf9e0540efbe5,
title = "Cohesin phosphorylation and mobility of SMC1 at ionizing radiation-induced DNA double-strand breaks in human cells",
abstract = "Cohesin, a hetero-tetrameric complex of SMC1, SMC3, Rad21 and Scc3, associates with chromatin after mitosis and holds sister chromatids together following DNA replication. Following DNA damage, cohesin accumulates at and promotes the repair of DNA double-strand breaks. In addition, phosphorylation of the SMC1/3 subunits contributes to DNA damage-induced cell cycle checkpoint regulation. The aim of this study was to determine the regulation and consequences of SMC1/3 phosphorylation as part of the cohesin complex. We show here that the ATM-dependent phosphorylation of SMC1 and SMC3 is mediated by H2AX, 53BP1 and MDC1. Depletion of RAD21 abolishes these phosphorylations, indicating that only the fully assembled complex is phosphorylated. Comparison of wild type SMC1 and SMC1S966A in fluorescence recovery after photo-bleaching experiments shows that phosphorylation of SMC1 is required for an increased mobility after DNA damage in G2-phase cells, suggesting that ATM-dependent phosphorylation facilitates mobilization of the cohesin complex after DNA damage.",
keywords = "Cell Cycle Proteins/metabolism, Chondroitin Sulfate Proteoglycans, Chromosomal Proteins, Non-Histone/metabolism, DNA Breaks, Double-Stranded/radiation effects, DNA Repair, G2 Phase, Humans, Multiprotein Complexes/metabolism, Phosphorylation, Protein Transport, Radiation, Ionizing",
author = "Christina Bauerschmidt and Michael Woodcock and Stevens, {David L} and Hill, {Mark A} and Kai Rothkamm and Thomas Helleday",
note = "Copyright {\textcopyright} 2010 Elsevier Inc. All rights reserved.",
year = "2011",
month = feb,
day = "1",
doi = "10.1016/j.yexcr.2010.10.021",
language = "English",
volume = "317",
pages = "330--7",
journal = "EXP CELL RES",
issn = "0014-4827",
publisher = "Academic Press Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Cohesin phosphorylation and mobility of SMC1 at ionizing radiation-induced DNA double-strand breaks in human cells

AU - Bauerschmidt, Christina

AU - Woodcock, Michael

AU - Stevens, David L

AU - Hill, Mark A

AU - Rothkamm, Kai

AU - Helleday, Thomas

N1 - Copyright © 2010 Elsevier Inc. All rights reserved.

PY - 2011/2/1

Y1 - 2011/2/1

N2 - Cohesin, a hetero-tetrameric complex of SMC1, SMC3, Rad21 and Scc3, associates with chromatin after mitosis and holds sister chromatids together following DNA replication. Following DNA damage, cohesin accumulates at and promotes the repair of DNA double-strand breaks. In addition, phosphorylation of the SMC1/3 subunits contributes to DNA damage-induced cell cycle checkpoint regulation. The aim of this study was to determine the regulation and consequences of SMC1/3 phosphorylation as part of the cohesin complex. We show here that the ATM-dependent phosphorylation of SMC1 and SMC3 is mediated by H2AX, 53BP1 and MDC1. Depletion of RAD21 abolishes these phosphorylations, indicating that only the fully assembled complex is phosphorylated. Comparison of wild type SMC1 and SMC1S966A in fluorescence recovery after photo-bleaching experiments shows that phosphorylation of SMC1 is required for an increased mobility after DNA damage in G2-phase cells, suggesting that ATM-dependent phosphorylation facilitates mobilization of the cohesin complex after DNA damage.

AB - Cohesin, a hetero-tetrameric complex of SMC1, SMC3, Rad21 and Scc3, associates with chromatin after mitosis and holds sister chromatids together following DNA replication. Following DNA damage, cohesin accumulates at and promotes the repair of DNA double-strand breaks. In addition, phosphorylation of the SMC1/3 subunits contributes to DNA damage-induced cell cycle checkpoint regulation. The aim of this study was to determine the regulation and consequences of SMC1/3 phosphorylation as part of the cohesin complex. We show here that the ATM-dependent phosphorylation of SMC1 and SMC3 is mediated by H2AX, 53BP1 and MDC1. Depletion of RAD21 abolishes these phosphorylations, indicating that only the fully assembled complex is phosphorylated. Comparison of wild type SMC1 and SMC1S966A in fluorescence recovery after photo-bleaching experiments shows that phosphorylation of SMC1 is required for an increased mobility after DNA damage in G2-phase cells, suggesting that ATM-dependent phosphorylation facilitates mobilization of the cohesin complex after DNA damage.

KW - Cell Cycle Proteins/metabolism

KW - Chondroitin Sulfate Proteoglycans

KW - Chromosomal Proteins, Non-Histone/metabolism

KW - DNA Breaks, Double-Stranded/radiation effects

KW - DNA Repair

KW - G2 Phase

KW - Humans

KW - Multiprotein Complexes/metabolism

KW - Phosphorylation

KW - Protein Transport

KW - Radiation, Ionizing

U2 - 10.1016/j.yexcr.2010.10.021

DO - 10.1016/j.yexcr.2010.10.021

M3 - SCORING: Journal article

C2 - 21056556

VL - 317

SP - 330

EP - 337

JO - EXP CELL RES

JF - EXP CELL RES

SN - 0014-4827

IS - 3

ER -