Estrogen and BRCA1 deficiency synergistically induce breast cancer mutation-related DNA damage

Estrogen (E2) is crucial for the development of breast cancer caused by BRCA1 mutation, and can increase the DNA damage in BRCA1-deficient cells. However, the mechanisms through which BRCA1 deficiency and E2 synergistically induce DNA damage remains unclear. In this study, we analyzed the distribution of DNA damage in E2-treated BRCA1-deficient cells. We detected DNA lesions in the vicinity of genes that are transcriptionally activated by estrogen receptor-alpha (ER). Loss of BRCA1 altered chromatin binding by ER, which significantly affected the distribution of DNA damage. Moreover, these changes were associated with the established mutations in BRCA1-mutant breast cancer. Taken together, our findings reveal a new mechanism underlying the DNA damage in breast cancer cells that is synergistically induced by BRCA1 deficiency and E2. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

Estrogen (E2) and BRCA1 deficiency synergistically induce DNA damage in breast cancer cells, possibly involving transcriptional activation of ER genes and changes in DNA damage distribution.