| Abstract | Breast cancer susceptibility gene 1 encoded BRCA1 and its heterodimeric partner BARD1 play an essential role in genomic stability by regulating DNA damage repair, cell-cycle checkpoints, and transcription regulation. Germline mutations in either of these genes expose individuals to a higher risk of developing breast and ovarian cancer. The Caenorhabditis elegans orthologs, brc-1 and brd-1, also regulate DNA damage repair and cell cycle checkpoints; however, their role in regulating gene transcription is still unknown. We hypothesized that, similar to humans, brc-1 of C. elegans regulates the expression of the cyp-13A gene subfamily, which are the homologs of the human estrogen metabolizing gene, CYP3A4. Here, we show the transcriptional regulation of brc-1 and brd-1 is conserved in worms. Using gene expression analysis, we found that knocking out brc-1 resulted in significant upregulation of four members of the cyp-13A subfamily, and loss of brd-1 function led to upregulation of six member of the cyp-13A subfamily. Our finding provides insights into how brc-1/brd-1 transcriptional regulation function is conserved in worms and further validates using C. elegans as a model system to investigate BRCA1 functions. |
