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Mol Cell. 2013 Jan 24;49(2):346-58. doi: 10.1016/j.molcel.2012.11.023. Epub 2012 Dec 27.

Dissection of DNA damage responses using multiconditional genetic interaction maps.

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1
Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.

Abstract

To protect the genome, cells have evolved a diverse set of pathways designed to sense, signal, and repair multiple types of DNA damage. To assess the degree of coordination and crosstalk among these pathways, we systematically mapped changes in the cell's genetic network across a panel of different DNA-damaging agents, resulting in ~1,800,000 differential measurements. Each agent was associated with a distinct interaction pattern, which, unlike single-mutant phenotypes or gene expression data, has high statistical power to pinpoint the specific repair mechanisms at work. The agent-specific networks revealed roles for the histone acetyltranferase Rtt109 in the mutagenic bypass of DNA lesions and the neddylation machinery in cell-cycle regulation and genome stability, while the network induced by multiple agents implicates Irc21, an uncharacterized protein, in checkpoint control and DNA repair. Our multiconditional genetic interaction map provides a unique resource that identifies agent-specific and general DNA damage response pathways.

PMID:
23273983
PMCID:
PMC3633480
DOI:
10.1016/j.molcel.2012.11.023
[Indexed for MEDLINE]
Free PMC Article

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