The Interplay between the Cellular Response to DNA Double-Strand Breaks and Estrogen

Lia Yedidia-Aryeh, Michal Goldberg

Research output: Contribution to journalReview articlepeer-review

Abstract

Cancer development is often connected to impaired DNA repair and DNA damage signaling pathways. The presence of DNA damage in cells activates DNA damage response, which is a complex cellular signaling network that includes DNA repair, activation of the cell cycle checkpoints, cellular senescence, and apoptosis. DNA double-strand breaks (DSBs) are toxic lesions that are mainly repaired by the non-homologous end joining and homologous recombination repair (HRR) pathways. Estrogen-dependent cancers, like breast and ovarian cancers, are frequently associated with mutations in genes that play a role in HRR. The female sex hormone estrogen binds and activates the estrogen receptors (ERs), ERα, ERβ and G-protein-coupled ER 1 (GPER1). ERα drives proliferation, while ERβ inhibits cell growth. Estrogen regulates the transcription, stability and activity of numerus DDR factors and DDR factors in turn modulate ERα expression, stability and transcriptional activity. Additionally, estrogen stimulates DSB formation in cells as part of its metabolism and proliferative effect. In this review, we will present an overview on the crosstalk between estrogen and the cellular response to DSBs. We will discuss how estrogen regulates DSB signaling and repair, and how DDR factors modulate the expression, stability and activity of estrogen. We will also discuss how the regulation of HRR genes by estrogen promotes the development of estrogen-dependent cancers.

Original languageAmerican English
Article number3097
JournalCells
Volume11
Issue number19
DOIs
StatePublished - Oct 2022

Keywords

  • DNA damage response (DDR)
  • DNA double-strand breaks (DSBs)
  • DSB repair
  • estrogen
  • estrogen receptor α (ERα)
  • homologous recombination repair (HRR)

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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