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Estrogen induces RAD51C expression and localization to sites of DNA damage
Author(s) -
Holz Marina K.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.799.1
Subject(s) - rad51 , carcinogenesis , cancer research , dna repair , estrogen receptor , genome instability , dna damage , biology , estrogen receptor alpha , homologous recombination , estrogen , cancer , breast cancer , microbiology and biotechnology , dna , genetics
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. Support or Funding Information NIH–CA151112; Atol Charitable Trust; LAM Foundation– 098P0113; American Cancer Society–RSG‐13‐287‐01‐TBE and National Cancer Center.