NuRD is recruited to DNA double-strand breaks, where it promotes RNF8/RNF168 histone ubiquitylation and accumulation of DNA repair factors (see also related paper by Larsen et al. in this issue)

Ahel

Albert Pastink

Aldo P. Solari

Bekker-Jensen

Chai

Clapier

Denslow

Doil

Dubrana

Godelieve Smeenk

Gong

Gottschalk

Grawunder

Haico van Attikum

Hans Vrolijk

Hoeijmakers

Huang

Huen

Ikura

Jazayeri

Khanna

Kolas

Larsen

Liang

Mailand

Morrison

Moynahan

Murr

Papamichos-Chronakis

Park

Pegoraro

Sartori

Seelig

Shiloh

Shim

Stewart

Stucki

Tsukuda

van Attikum

van Haaften

Wang

Wouter W. Wiegant

Zhang

English

PubMed

Crossref

The NuRD chromatin–remodeling complex regulates signaling and repair of DNA damage

Cells respond to ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) by orchestrating events that coordinate cell cycle progression and DNA repair. How cells signal and repair DSBs is not yet fully understood. A genome-wide RNA interference screen in Caenorhabditis elegans identified egr-1 as a factor that protects worm cells against IR. The human homologue of egr-1, MTA2 (metastasis-associated protein 2), is a subunit of the nucleosome-remodeling and histone deacetylation (NuRD) chromatin-remodeling complex. We show that knockdown of MTA2 and CHD4 (chromo-domain helicase DNA-binding protein 4), the catalytic subunit (adenosine triphosphatase [ATPase]) of NuRD, leads to accumulation of spontaneous DNA damage and increased IR sensitivity. MTA2 and CHD4 accumulate in DSB-containing chromatin tracks generated by laser microirradiation. Directly at DSBs, CHD4 stimulates RNF8/RNF168-dependent formation of ubiquitin conjugates to facilitate the accrual of RNF168 and BRCA1. Finally, we show that CHD4 promotes DSB repair and checkpoint activation in response to IR. Thus, the NuRD chromatin-remodeling complex is a novel regulator of DNA damage responses that orchestrates proper signaling and repair of DSBs.DNA repair mechanism

Smeenk, G.

Wiegant, W.W.

Vrolijk, H.

Solari, A.P.

Pastink, A.

Attikum, H. van

Leiden University Scholary Publications

The NuRD chromatin-remodeling complex regulates signaling and repair of DNA damage

a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities.

Accumulation of Pax2 transactivation domain interaction protein (PTIP) at sites of DNA breaks via RNF8-dependent pathway is required for cell survival after DNA damage.

Ageing-related chromatin defects through loss of the NURD complex.

ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks.

checkpoints after ionizing irradiation.

Deacetylation of p53 modulates its effect on cell growth and apoptosis.

Distinct roles of chromatin-associated proteins MDC1 and 53BP1 in mammalian double-strand break repair.

DNA ligase IV is essential for V(D)J recombination and DNA doublestrand break repair in human precursor lymphocytes.

Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase.

Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1.

Poly(ADP-ribosyl)ation directs recruitment and activation of an ATPdependent chromatin remodeler.

RSC functions as an early double-strand-break sensor in the cell’s response to DNA damage.

The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation. Arthritis Rheum. 38:1389– 1399. doi:10.1002/art.1780381006

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2935570

The NuRD chromatin–remodeling complex regulates signaling and repair of DNA damage

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Leiden University Scholary Publications