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RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells

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RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells. / Piwko, W.; Olma, M.H.; Held, M.; Pedrioli, P.G.A.; Gerlich, D.W.; Peter, M.; Bianco, J.N.; Pasero, P.; Hofmann, K.

In: EMBO Journal, Vol. 29, No. 24, 15.12.2010, p. 4210-4222.

Research output: Contribution to journalArticle

Harvard

Piwko, W, Olma, MH, Held, M, Pedrioli, PGA, Gerlich, DW, Peter, M, Bianco, JN, Pasero, P & Hofmann, K 2010, 'RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells' EMBO Journal, vol 29, no. 24, pp. 4210-4222., 10.1038/emboj.2010.304

APA

Piwko, W., Olma, M. H., Held, M., Pedrioli, P. G. A., Gerlich, D. W., Peter, M., ... Hofmann, K. (2010). RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells. EMBO Journal, 29(24), 4210-4222. 10.1038/emboj.2010.304

Vancouver

Piwko W, Olma MH, Held M, Pedrioli PGA, Gerlich DW, Peter M et al. RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells. EMBO Journal. 2010 Dec 15;29(24):4210-4222. Available from: 10.1038/emboj.2010.304

Author

Piwko, W.; Olma, M.H.; Held, M.; Pedrioli, P.G.A.; Gerlich, D.W.; Peter, M.; Bianco, J.N.; Pasero, P.; Hofmann, K. / RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells.

In: EMBO Journal, Vol. 29, No. 24, 15.12.2010, p. 4210-4222.

Research output: Contribution to journalArticle

Bibtex - Download

@article{11515bd8e8f14cb0a68e72a1fcecd5f2,
title = "RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells",
author = "W. Piwko and M.H. Olma and M. Held and P.G.A. Pedrioli and D.W. Gerlich and M. Peter and J.N. Bianco and P. Pasero and K. Hofmann",
year = "2010",
doi = "10.1038/emboj.2010.304",
volume = "29",
number = "24",
pages = "4210--4222",
journal = "EMBO Journal",
issn = "0261-4189",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells

A1 - Piwko,W.

A1 - Olma,M.H.

A1 - Held,M.

A1 - Pedrioli,P.G.A.

A1 - Gerlich,D.W.

A1 - Peter,M.

A1 - Bianco,J.N.

A1 - Pasero,P.

A1 - Hofmann,K.

AU - Piwko,W.

AU - Olma,M.H.

AU - Held,M.

AU - Pedrioli,P.G.A.

AU - Gerlich,D.W.

AU - Peter,M.

AU - Bianco,J.N.

AU - Pasero,P.

AU - Hofmann,K.

PY - 2010/12/15

Y1 - 2010/12/15

N2 - Cullin 4 (Cul4)-based ubiquitin ligases emerged as critical regulators of DNA replication and repair. Over 50 Cul4-specific adaptors (DNA damage-binding 1 (Ddb1)-Cul4-associated factors; DCAFs) have been identified and are thought to assemble functionally distinct Cul4 complexes. Using a live-cell imaging-based RNAi screen, we analysed the function of DCAFs and Cul4-linked proteins, and identified specific subsets required for progression through G1 and S phase. We discovered C6orf167/Mms22-like protein (Mms22L) as a putative human orthologue of budding yeast Mms22, which, together with cullin Rtt101, regulates genome stability by promoting DNA replication through natural pause sites and damaged templates. Loss of Mms22L function in human cells results in S phase-dependent genomic instability characterised by spontaneous double-strand breaks and DNA damage checkpoint activation. Unlike yeast Mms22, human Mms22L does not stably bind to Cul4, but is degraded in a Cul4-dependent manner and upon replication stress. Mms22L physically and functionally interacts with the scaffold-like protein Nfkbil2 that co-purifies with histones, several chromatin remodelling and DNA replication/repair factors. Together, our results strongly suggest that the Mms22L-Nfkbil2 complex contributes to genome stability by regulating the chromatin state at stalled replication forks. © 2010 European Molecular Biology Organization | All Rights Reserved.

AB - Cullin 4 (Cul4)-based ubiquitin ligases emerged as critical regulators of DNA replication and repair. Over 50 Cul4-specific adaptors (DNA damage-binding 1 (Ddb1)-Cul4-associated factors; DCAFs) have been identified and are thought to assemble functionally distinct Cul4 complexes. Using a live-cell imaging-based RNAi screen, we analysed the function of DCAFs and Cul4-linked proteins, and identified specific subsets required for progression through G1 and S phase. We discovered C6orf167/Mms22-like protein (Mms22L) as a putative human orthologue of budding yeast Mms22, which, together with cullin Rtt101, regulates genome stability by promoting DNA replication through natural pause sites and damaged templates. Loss of Mms22L function in human cells results in S phase-dependent genomic instability characterised by spontaneous double-strand breaks and DNA damage checkpoint activation. Unlike yeast Mms22, human Mms22L does not stably bind to Cul4, but is degraded in a Cul4-dependent manner and upon replication stress. Mms22L physically and functionally interacts with the scaffold-like protein Nfkbil2 that co-purifies with histones, several chromatin remodelling and DNA replication/repair factors. Together, our results strongly suggest that the Mms22L-Nfkbil2 complex contributes to genome stability by regulating the chromatin state at stalled replication forks. © 2010 European Molecular Biology Organization | All Rights Reserved.

UR - http://www.scopus.com/inward/record.url?scp=78650257875&partnerID=8YFLogxK

U2 - 10.1038/emboj.2010.304

DO - 10.1038/emboj.2010.304

M1 - Article

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 24

VL - 29

SP - 4210

EP - 4222

ER -

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