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Expression analysis using DNA microarrays demonstrates that E2F-1 up-regulates expression of DNA replication genes including replication protein A2

Oncogene volume 20, pages 1379–1387 (2001)Cite this article

Abstract

The transcription factor E2F-1 plays a pivotal role in the regulation of G1/S transition in higher eukaryotes cell cycle. We used a cell line containing an inducible E2F-1 and oligonucleotide microarray analysis to identify novel E2F target genes. We show that E2F-1 up-regulates the expression of a number of genes coding for components of the DNA replication machinery. Among them is the gene coding for the 32 Kd subunit of replication protein A (RPA2). Replication protein A is the most abundant single strand DNA binding complex and it is essential for DNA replication. We demonstrate that RPA2 is a novel E2F target gene whose expression can be directly regulated by E2F-1 via E2F binding sites in its promoter. In addition, expression of Topoisomerase IIα and subunit IV of DNA polymerase α is also up-regulated upon E2F-1 induction. Taken together, these results provide novel links between components of the DNA replication machinery and the cell growth regulatory pathway involving the Rb tumor suppressor and E2F.

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Acknowledgements

We thank Drs WG Kaelin Jr and PD Adams for cells lines and Dr D Givol for reagents and critical reading of the manuscript. We thank Dr Shirley Horn-Saban for excellent technical assistance with DNA microarray analysis. This work was supported in part by grants from the Israel cancer Association (ICA), Minerva Foundation (Germany), the Israel Cancer Research Fund (ICRF) and Yad Abraham Research Center for Diagnostics and Therapy. D Ginsburg is an incumbent of the Recanati Career Development chair of cancer research.

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  1. Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel

    Yael Kalma, Lea Marash, Yocheved Lamed & Doron Ginsberg

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  1. Yael Kalma
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Kalma, Y., Marash, L., Lamed, Y. et al. Expression analysis using DNA microarrays demonstrates that E2F-1 up-regulates expression of DNA replication genes including replication protein A2. Oncogene 20, 1379–1387 (2001). https://doi.org/10.1038/sj.onc.1204230

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