Selective control of tRNA gene transcription by steroid receptors and BRCA1

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BRCA1 is an important tumour suppressor protein with roles in DNA repairand transcription. BRCA1 binds many tRNA genes, but its role there isunknown. This project will test if repression of tRNA gene transcription byBRCA1 is part of its function as a tumour suppressor.Oestrogen drives proliferation of breast cells and its receptor is targeted bythe widely-used drug tamoxifen. Oestrogen receptor binds and activatestRNA genes, effects that are countered by tamoxifen. Progesterone can alsoantagonize the mitogenic effects of oestrogen. The progesterone receptorwas recently found to interact with RNA polymerase III at specific tRNAgenes and repress their expression. We will investigate how oestrogen andprogesterone receptors select tRNA genes and influence transcription atthese sites.This project will provide extensive training in molecular interactions betweenkey genes and factors with massive impact on cell biology and human health.