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. 2018 May 29;5(4):e1465014.
doi: 10.1080/23723556.2018.1465014. eCollection 2018.

Ewing sarcoma fusion oncogene: At the crossroads of transcription and DNA damage response

Aparna Gorthi  1   2 , Alexander J R Bishop  1   2   3
Affiliations

Ewing sarcoma fusion oncogene: At the crossroads of transcription and DNA damage response

Aparna Gorthi et al. Mol Cell Oncol. .
No abstract available

Keywords: BRCA1; EWSR1; Ewing sarcoma; R-loops; transcription.

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Figures

Figure 1.
Figure 1.
Altered control of transcription in Ewing sarcoma. Transcription elongation is triggered by cyclin dependent kinase 9 (CDK9) dependent phosphorylation of RNA Polymerase II (RNAPII) C-terminal domain. EWS RNA binding protein 1 (EWSR1) inhibits this phosphorylation event thereby controlling transcription rates. BRCA1, DNA repair associated protein (BRCA1) is associated with hyper-phosphorylated RNAPII under basal conditions but is released upon infliction of DNA damage to sites of break repair. However in Ewing sarcoma, EWS-FLI1 allows aberrant transcription by lifting EWSR1 dependent inhibition of CDK9 activity resulting in R-loop accumulation. This, in turn, prevents BRCA1 release from transcription complexes thus impairing homologous recombination repair of exogenously induced double strand breaks.
See this image and copyright information in PMC

References

    1. Delattre O. Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G, et al. . Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992;359:162–165. - PubMed
    1. Rodriguez-Galindo C, Spunt SL, Pappo AS. Treatment of Ewing sarcoma family of tumors: Current status and outlook for the future. Med Pediatric Oncol. 2003;40:276–287. - PubMed
    1. Gorthi A, Romero JC, Loranc E, Cao L, Lawrence LA, Goodale E, Iniguez AB, Bernard X, Masamsetti VP, Roston S, et al. . EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma. Nature. 2018;555:387–391. - PMC - PubMed
    1. Ljungman M, Zhang F. Blockage of RNA polymerase as a possible trigger for u.v. light-induced apoptosis. Oncogene. 1996;13:823–831. - PubMed
    1. Krum SA, Miranda GA, Lin C, Lane TF. BRCA1 Associates with Processive RNA Polymerase II. J Biol Chem. 2003;278:52012–52020. - PubMed