Dec 15, 2015

Ewing sarcoma breakpoint region 1 prevents transcription-associated genome instability

BioRxiv : the Preprint Server for Biology
Nitish MittalMihaela Zavolan

Abstract

Ewing Sarcoma break point region 1 (EWSR1) is a multi-functional RNA-binding protein that is involved in many cellular processes, from gene expression to RNA processing and transport. Translocations into its locus lead to chimeric proteins with tumorigenic activity, that lack the RNA binding domain. With crosslinking and immunoprecipitation we have found that EWSR1 binds to intronic regions that are present in polyadenylated nuclear RNAs, which include the translocation-prone region of its own locus. Reduced EWSR1 expression leads to gene expression changes that indicate reduced proliferation. By fluorescence in situ hybridization (FISH) with break-apart probes that flanked the translocation-prone region within the EWSR1 locus we found that reduced EWSR1 expression increases the frequency of split signals, indicative of DNA double strand breaks (DSB). The response in phosphorylated histone H2AX and p53-binding protein 1 (53BP1) double-stained foci to the topoisomerase poison camptothecin in cells treated with a control shRNA and with sh-EWSR1 further suggests that EWSR1 functions in the prevention of DNA DSBs. Our data reveal a new function of the EWSR1 member of the FET family and suggest a connection between the RNA-binding a...Continue Reading

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Mentioned in this Paper

EWSR1 wt Allele
Tumorigenicity
Fluorescent in Situ Hybridization
Protein Binding
Cellular Process
Genome
DNA Repair
Transcription, Genetic
RNA, Polyadenylated
RNA-Binding Protein EWS

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