Oncology & Cancer

The full-length human BRCA2 protein binding to DNA was observed for the first time using a single molecule microscope.

Researchers from Yale Cancer Center and the University of California, Davis, have for the first time visualized the full-length human BRCA2 protein at the single-molecule level using a self-built inverted microscope equipped with laser optical tweezers to capture DNA.

The likelihood of a person developing cancer over their lifetime can be significantly increased by mutations in the BRCA2 breast cancer susceptibility gene. A significant portion of heritable cancer is caused by a BRCA gene mutation, which affects about one in every 400 individuals. In the Proceedings of the National Academy of Sciences, the study was released on March 28.

According to Ryan Jensen, Ph.D., a member of the Yale Cancer Center and co-author of the study, “If you carry a BRCA mutation, you have this incredibly high risk for breast and ovarian cancer, as well as for men, prostate and pancreatic cancer.”. D., who is also an adjunct professor of therapeutic radiology at Yale School of Medicine.

“If you have a BRCA mutation, you have an exceedingly high risk of breast and ovarian cancer, as well as male, prostate, and pancreatic cancer,”

Co-author of the paper, Ryan Jensen, Ph.D.,

When a BRCA2 mutation is found in a patient, it is crucial that we comprehend it at the molecular level. My lab is completely invested in understanding the BRCA2 protein in all its facets, including why, if the BRCA2 protein does not perform its function, that failure results in cancer.”.

Instructions for creating a protein that functions as a tumor suppressor are provided by the BRCA2 gene. Tumor suppressor proteins aid in limiting uncontrolled or excessive cell growth and division. According to Dr. Dot Jensen, the goal of this experiment was to learn more about how the BRCA2 protein binds to and interacts with DNA, one molecule at a time. This “visual biochemistry” method is similar to watching a movie in a theater while learning how proteins bind and interact with DNA in real time.

Since BRCA2 is a DNA repair protein, it fixes DNA damage. In particular, human cells have several different pathways for repairing DNA double-strand breaks. According to Dr. Jensen, BRCA2 specifically functions in the homologous recombination pathway.

“By understanding how BRCA2 functions at the molecular level, we will have more knowledge to develop new strategies that may one day assist BRCA mutation carriers who either don’t respond or relapse on present standard-of-care therapies. The better, according to Dr. Jensen, is more knowledge.

More information: Jason C. Bell et al, BRCA2 chaperones RAD51 to single molecules of RPA-coated ssDNA, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2221971120

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