Estrogen induces RAD51C expression and localization to sites of DNA damage

Homologous recombination (HR) is a conserved process that maintains genome stability and cell survival by repairing DNA double‐strand breaks (DSBs). The RAD51‐related family of proteins is involved in repair of DSBs, consequently, deregulation of RAD51 in human cells causes chromosomal rearrangements and stimulates tumorigenesis. RAD51C in particular has been identified as a potential tumor suppressor and a breast and ovarian cancer susceptibility gene. Recent studies implicated estrogen as a DNA‐damaging agent that causes DSBs. We found that in estrogen receptor (ER)α‐positive breast cancer cells, estrogen transcriptionally regulates RAD51C expression in ERα‐dependent mechanism. Moreover, estrogen induces RAD51C assembly into nuclear foci at DSBs, which is a precursor to RAD51 complex recruitment to the nucleus. These findings provide insight into the mechanism of genomic instability in ERα‐positive breast cancer. We propose that in normal breast epithelia, estrogen‐induced DNA damage is compensated by estrogenic activation of expression of DNA repair proteins, such as RAD51C. Conversely, individuals with mutations in RAD51C would be more susceptible to accumulation of DNA damage, leading to tumorigenesis and cancer progression.

• Publication year

  2016

• Venue

  Cell Cycle

• Publication date

  2016-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1080/15384101.2016.1241927PMID 27753535PMCID PMC5176134
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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