A new study recently published in the journal Proceedings of the National Academy of Sciences opens a window on key findings regarding BRCA1. As it turns out, this gene is extremely important in protecting against breast and ovarian cancer. Discovery by scientists at the Center for Theoretical Biological Physics reveals an underlying rule that glues DNA transcription together. If confirmed, this finding would have major ramifications for the field’s understanding of genetic mistakes.
The initial work, led by now-postdoctoral fellow Anjali Midha, examined the nucleotide sequence of the BRCA1 gene. The proper functioning of this gene is an absolute must for a healthy cell and the prevention of malignancies. The team took a hard look at how transcription errors can be sequence-dependent. This leads to an increase in the likelihood of creating premature stop codons, which hinder protein synthesis and lead to non-functioning proteins.
Research demonstrates that the identity of the two nucleotides immediately downstream of a transcription start site is particularly important. That has a big impact on the error rate when transcribing. If valid, the finding would indicate that specific DNA sequences in the BRCA1 gene are more prone to produce transcription mistakes. This has significant implications for an individual’s risk of developing cancer.
To further their analysis, the scientists were able to develop a new 3D-model of DNA. This strategy enabled them to study how changes in nucleotide sequence affect transcriptional fidelity. Beyond just BRCA1, this study has major implications. By revealing the principles underlying these rules, we can learn about the ways genetic instructions regulate cellular activity.
Each living cell has to be able to read its genetic code properly—a string of chemical letters that determine thousands of biological functions. This study adds important details that help broaden our knowledge of BRCA1. It further paves the way for subsequent studies aimed at correcting genetic mistakes that cause diseases.
We are especially grateful to Michael Ströck for his contribution to this study for uploading an image of DNA. Photo credit Wikimedia, available under the GNU Free Documentation License. I wrote about these findings in this study on the article on phys.org for July 9, 2025. It is connected to the DOI 10.1073/pnas.2505040122.