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IKK and NF-kappa B-mediated regulation of Claspin impacts on ATR checkpoint function

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IKK and NF-kappa B-mediated regulation of Claspin impacts on ATR checkpoint function. / Kenneth, Niall Steven; Mudie, Sharon; Rocha, Sonia.

In: EMBO Journal, Vol. 29, No. 17, 01.09.2010, p. 2966-2978.

Research output: Contribution to journalArticle

Harvard

Kenneth, NS, Mudie, S & Rocha, S 2010, 'IKK and NF-kappa B-mediated regulation of Claspin impacts on ATR checkpoint function' EMBO Journal, vol 29, no. 17, pp. 2966-2978.

APA

Kenneth, N. S., Mudie, S., & Rocha, S. (2010). IKK and NF-kappa B-mediated regulation of Claspin impacts on ATR checkpoint function. EMBO Journal, 29(17), 2966-2978doi: 10.1038/emboj.2010.171

Vancouver

Kenneth NS, Mudie S, Rocha S. IKK and NF-kappa B-mediated regulation of Claspin impacts on ATR checkpoint function. EMBO Journal. 2010 Sep 1;29(17):2966-2978.

Author

Kenneth, Niall Steven; Mudie, Sharon; Rocha, Sonia / IKK and NF-kappa B-mediated regulation of Claspin impacts on ATR checkpoint function.

In: EMBO Journal, Vol. 29, No. 17, 01.09.2010, p. 2966-2978.

Research output: Contribution to journalArticle

Bibtex - Download

@article{8a72f30349684549a13332a7496a53d5,
title = "IKK and NF-kappa B-mediated regulation of Claspin impacts on ATR checkpoint function",
author = "Kenneth, {Niall Steven} and Sharon Mudie and Sonia Rocha",
year = "2010",
volume = "29",
number = "17",
pages = "2966--2978",
journal = "EMBO Journal",
issn = "0261-4189",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - IKK and NF-kappa B-mediated regulation of Claspin impacts on ATR checkpoint function

A1 - Kenneth,Niall Steven

A1 - Mudie,Sharon

A1 - Rocha,Sonia

AU - Kenneth,Niall Steven

AU - Mudie,Sharon

AU - Rocha,Sonia

PY - 2010/9/1

Y1 - 2010/9/1

N2 - <p>In response to replication stress, Claspin mediates the phosphorylation and activation of Chk1 by ATR. Claspin is not only necessary for the propagation of the DNA-damage signal, but its destruction by the ubiquitin-proteosome pathway is required to allow the cell to continue the cell cycle allowing checkpoint recovery. Here, we demonstrate that both the NF-kappa B family of transcription factors and their upstream kinase IKK can regulate Claspin levels by controlling its mRNA expression. Furthermore, we show that c-Rel directly controls Claspin gene transcription. Disruption of IKK and specific NF-kappa B members impairs ATR-mediated checkpoint function following DNA damage. Importantly, hyperactivation of IKK results in a failure to inactivate Chk1 and impairs the recovery from the DNA checkpoint. These results uncover a novel function for IKK and NF-kappa B modulating the DNA-damage checkpoint response, allowing the cell to integrate different signalling pathways with the DNA-damage response. The EMBO Journal (2010) 29, 2966-2978. doi: 10.1038/emboj.2010.171; Published online 23 July 2010</p>

AB - <p>In response to replication stress, Claspin mediates the phosphorylation and activation of Chk1 by ATR. Claspin is not only necessary for the propagation of the DNA-damage signal, but its destruction by the ubiquitin-proteosome pathway is required to allow the cell to continue the cell cycle allowing checkpoint recovery. Here, we demonstrate that both the NF-kappa B family of transcription factors and their upstream kinase IKK can regulate Claspin levels by controlling its mRNA expression. Furthermore, we show that c-Rel directly controls Claspin gene transcription. Disruption of IKK and specific NF-kappa B members impairs ATR-mediated checkpoint function following DNA damage. Importantly, hyperactivation of IKK results in a failure to inactivate Chk1 and impairs the recovery from the DNA checkpoint. These results uncover a novel function for IKK and NF-kappa B modulating the DNA-damage checkpoint response, allowing the cell to integrate different signalling pathways with the DNA-damage response. The EMBO Journal (2010) 29, 2966-2978. doi: 10.1038/emboj.2010.171; Published online 23 July 2010</p>

KW - Chk1

KW - Claspin

KW - IKK

KW - NF-kappa B

KW - CELL-CYCLE

KW - CHK1 ACTIVATION

KW - GENE-EXPRESSION

KW - BREAST-CANCER

KW - DEGRADATION

KW - RECOVERY

KW - PHOSPHORYLATION

KW - DOWNSTREAM

KW - INHIBITION

KW - PATHWAYS

U2 - 10.1038/emboj.2010.171

DO - 10.1038/emboj.2010.171

M1 - Article

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 17

VL - 29

SP - 2966

EP - 2978

ER -

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