In a surprising twist akin to a classic narrative of foes turned allies, researchers at Cornell University have uncovered a pivotal role for DNA packaging structures known as nucleosomes. Once considered obstacles to gene expression, these structures are now recognized for their crucial function in mitigating torsional stress in DNA strands, thereby facilitating the decoding of genetic information.
The breakthrough, led by Michelle Wang, the James Gilbert White Distinguished Professor of the Physical Sciences at Cornell’s College of Arts and Sciences, was published on December 18 in the journal Science. According to Wang, “If gene expression does not proceed properly, it will lead to all kinds of problems. Abnormal cellular growth, cancer development, and other disorders – they’re all interconnected.”
The Mechanics of Gene Expression
Gene expression, a fundamental biological process, involves the transcription of DNA into RNA, which then guides protein synthesis. This process is akin to decoding an instruction manual, where the DNA serves as the source of genetic information. However, the helical structure of DNA presents a unique challenge. As the motor enzyme RNA polymerase transcribes the DNA, it induces torsional stress, much like the tension in a tightly wound rope.
Traditionally, nucleosomes have been viewed as barriers that RNA polymerase must overcome. These nucleosomes, which organize and compact DNA into chromatin, were thought to hinder the smooth progress of transcription. Yet, Wang’s team has demonstrated that nucleosomes actually play a supportive role by alleviating torsional stress during transcription.
Innovative Research Tools
To unravel this complex interaction, Wang’s lab developed cutting-edge tools such as the angular optical trap and magnetic tweezers. These instruments allow researchers to manipulate and measure DNA at a molecular level, providing insights into the dynamics of transcription.
Through these tools, the team discovered that nucleosomes wrap DNA in a left-handed spiral, counteracting the right-handed twist of the DNA double helix. This opposing orientation helps relieve the torsional stress that accumulates as RNA polymerase advances along the DNA strand.
Additional Molecular Assistance
The research also highlights the role of topoisomerases, enzymes that act like molecular scissors. These enzymes make temporary cuts in the DNA to release torsional stress and then swiftly repair the breaks, further facilitating the transcription process.
“As polymerase moves forward, the chromatin becomes a torsional buffer. It releases that stress to allow transcription to move forward. We are really excited by this discovery,” Wang said.
Implications and Future Directions
The findings underscore the intricate interplay between physical properties of biomolecules and biological functions. Wang, who has been reappointed as a Howard Hughes Medical Institute Investigator, is optimistic about the potential for further discoveries in this field. “We can take this in so many directions, things like nucleosome modifications and remodeling that could change chromatin mechanical properties, which then change how polymerase can go through a nucleosome,” she explained.
The research team, which includes co-authors from institutions such as Johns Hopkins University and the National Cancer Institute, aims to explore new questions about gene expression and its regulation. Their work is supported by the Howard Hughes Medical Institute and the National Institutes of Health.
As the scientific community continues to delve into the complexities of gene expression, the newfound understanding of nucleosomes as facilitators rather than hindrances marks a significant advancement. This discovery not only enriches our comprehension of genetic processes but also opens avenues for potential therapeutic interventions in diseases linked to gene expression anomalies.
