A landmark study published in the journal Nature provides new insight into the function of an enzyme related to the BRCA1 breast cancer protein. The study by a team at Penn State University is the first to produce a detailed working image of an enzyme in the Polycomb Repressive Complex 1 (PRC1) – a group that regulates cell development and is associated with many types of cancer.
Enzymes like PRC1 turn on or turn off the activity of genes in a cell by manipulating individual chromosome units called nucleosomes. “The nucleosome is a key target of the enzymes that conduct genetic processes critical for life,” said Song Tan, professor of biochemistry and molecular biology at Penn State University and the leader of the study’s research team.
The Penn State scientists obtained the first crystal structure of a gene regulation enzyme while it is working on a nucleosome. The image reveals previously unknown information about how the enzyme attaches to its nucleosome target. Before this study, scientists had been unable to picture exactly how cancer-related enzymes in the PRC1 group interacted with a nucleosome to control gene activity. The study is also the first to determine the crystal structure of a multisubunit protein complex bound to a nucleosome, which itself is a complex assembly of DNA and 4 histone proteins.
This image reveals the crystal structure of the PRC1 enzyme (yellow, blue and red) bound to the nucleosome (DNA in light blue, histone proteins in purple, light green, light yellow and pink). Credit: Song Tan lab, Penn State University.
Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome, Robert K. McGinty, Ryan C. Henrici & Song Tan, Nature, doi:10.1038/nature13890, published online 29 October 2014.