An international collective of researchers is delivering new insights into why having multiple psychiatric disorders is the norm rather than the exception. In a study published today in the journal Nature, the team provides the largest and most detailed analysis to date on the genetic roots shared among 14 conditions.

The study is the latest effort from the Psychiatric Genomics Consortium’s Cross-Disorder Working Group, co-chaired by Kenneth Kendler, M.D., a professor in the Department of Psychiatry at Virginia Commonwealth University’s School of Medicine, and Jordan Smoller, M.D., a professor in the Department of Psychiatry at Harvard Medical School.

The majority of people diagnosed with a psychiatric disorder will ultimately be diagnosed with a second or third disorder in their lifetime, creating challenges for defining and treating these conditions. While a person’s environment and lived experience influence their risk for developing multiple disorders, their genetic makeup can also play a significant role.

Structural insights into PRC2 function in development and disease.

Polycomb repressive complex 2 (PRC2) is a central epigenetic regulator of developmental gene repression that displays remarkable complexity arising from multiple molecular layers.

Enzyme catalysis and chromatin targeting form the basis of the common and distinct functions of PRC2.1 and PRC2.2, serving as focal points in the cellular regulation of PRC2 activity under both physiological and pathological contexts.

Structural biology has begun to clarify the molecular mechanisms underlying key functions of PRC2 and uncover new modes of regulation, with much still remaining to be understood about the elaborate system of PRC2-mediated gene control. https://sciencemission.com/PRC2-function-in-development-and-disease

Polycomb repressive complex 2 (PRC2) is a key epigenetic enzyme complex that mediates developmental gene repression mainly by depositing the repressive H3K27me3 histone mark. PRC2 operates through its distinct forms, PRC2.1 and PRC2.2, each defined by unique accessory subunits, with additional complexity introduced by other molecular variants such as developmentally regulated homologs and isoforms. PRC2 function is primarily dictated by its enzymatic activity and chromatin recruitment, both of which are rigorously controlled during development and can be dysregulated by disease-associated mutations and oncoproteins. Structural biology has begun to provide important mechanistic insights into various aspects of PRC2 assembly, catalysis, chromatin targeting, and cellular regulation at atomic resolution, addressing several longstanding questions about the Polycomb repression system.

An international research team has identified a human protein, ANKLE1, as the first DNA-cutting enzyme (nuclease) in mammals capable of detecting and responding to physical tension in DNA. This “tension-sensing” mechanism plays a vital role in maintaining genetic integrity during cell division—a process that, when disrupted, can lead to cancer and other serious diseases.

The study, titled “ANKLE1 processes chromatin bridges by cleaving mechanically stressed DNA,” published in Nature Communications, represents a major advance in the understanding of cellular DNA protection.

The research was conducted through a cross-disciplinary collaboration between Professor Gary Ying Wai Chan’s laboratory at the School of Biological Sciences, The University of Hong Kong (HKU) and Dr. Artem Efremov’s biophysics team at Shenzhen Bay Laboratory (SZBL), with additional contributions from researchers at the Hong Kong University of Science and Technology (HKUST) and the Francis Crick Institute in London.