The nature of the corona kinetochore was later described

Exciting the search for a well -kept secret: The nature of the corona kinetochore has been revealed

The advanced cryo-EM design captures the critical features of the ROD-Zwilch-ZW10 (RZZ) complex. Available: MPI of Molecular Physiology

During signaling division in the mother cell, the 23 chromosomes that make up the human genome must first be copied and then given to two new daughter cells. At the very least in healthy cells, there is no trace of the lesion, no chromosome is lost. Not so in malignant cells, where chromosome separation errors result in a constant flow of new genetic traits that support metastatic growth and are resistant to chemotherapy. A protein system called a kinetochore is used in the chromosome transport system. On an important interdisciplinary field trip, the teams of Andrea Musacchio and Stefan Raunser at the Max Planck Department of Molecular Physiology studied the outer layer of this building, the corona kinetochore. With the help of cryo electron microscopy and protein reconstruction, they demonstrated the structural structure of the corona’s main plate, the RZZ complex, and described the nature of the corona group. . Their result is to shed light on the molecular origins of genome inheritance across generations.

The cell division makes our body, supplying all the cells in our flesh and organs, from the skin to the stomach, from the blood to the brain. It not only allows these bodies to grow, but to regenerate with new cells as needed. Cell division begins with the re -creation of chromosomes, which carry the three billion nucleotides of the human genome. The regenerated chromosomes are delivered to the girl’s cells in a process called mitosis. During mitosis, the chromosomes first contain a network of spindle -like structures called the mitotic spindle. After placing them in a highly choreographed sequence, the spindle separates the chromosomes on the other side, while two cells are made out of one, to get each other. the exact copy of the genome. The smallest errors in this process will have physiological consequences.

It’s a multilayered appeal

The kinetochore is the point at which chromosomes connect with the spin, and is therefore heavily involved in the process of chromosome alignment and fragmentation. It is a complex multilayered protein complex. “It’s really hard to understand the kinetochores, because there are a number of layers, each made with concrete blocks,” Musacchio said. “The outermost layer, the corona, holds one of the most interesting secrets of the kinetochore.

As in previous studies, Musacchio’s laboratory covered the structure and function of different parts of kinetochores and how they attach chromosomes to microtubules. To achieve this, the company took a reduction approach called biochemical reconstitution. They made individual pieces of protein cells out of the cell, in a test tube. Then, they reassemble them piece by piece to create a nearly complete kinetochore that they can learn independently, in a controlled environment that is easy to differentiate with the complexity of the environment. cell.

Requesting the same design, the expert team of two postdocs, Tobias Raisch and Giuseppe Ciossani, both Ph.D. The students, Ennio d’Amico and Verena Cmentowski, and other colleagues were able to reconstruct the corona kinetochore. They showed that only two were sufficient for it: the ROD-Zwilch-ZW10 (RZZ) protein complex and the Spindly protein, which is important in the interaction of the kinetochore with microtubules. The corona is simply grafted onto kinetochores, and the methods to limit its growth in these structures remain an important unresolved question. By replicating the process in vitro, scientists were able to identify an enzyme, kinase MPS1, as a major promoter of the RZZ corona group in the kinetochore.

One foot close to the crown

Electron microscopy (EM) has also been involved in the study of kinetochores since the 1960s, but it is not until now that the development of techniques that allow this technology to detect building blocks in the atomic scale. “In 2017, we performed the first 3D model of the RZZ complex by cryo-EM,” says Raunser. “However, at the 1 nm resolution of this first sample, it is not possible to observe the best molecular details related to biological activity.”

The reorganization was improved until the atomic particles were released, later explaining how the RZZ particles interacted with themselves and Spindly to propagate the corona group in a polymer. large surrounding the kinetochore. “Our work is the crowning glory of the first studies on the corona kinetochore, this time to give us a framework to understand the critical moment of cell division when the coronary artery occurs. chromosomes into microtubules that cannot be altered ”concludes Musacchio. Future studies of the team will attempt to integrate the corona into new kinetochores, moving to a new critical role in the reconstruction of chromosome separation in vitro, a goal of major research to illuminate the source of the great process of life.

The research is published in The EMBO Journal.

Performance of the basic engineering of cell division

More information:
Tobias Raisch et al, Design of the complex RZZ and molecular basis of Spindly-driven corona assembly in human kinetochores, The EMBO Journal (2022). DOI: 10.15252 / embj.2021110411

Presented by Max Planck Institute of Molecular Physiology

Directions: Kinetochore corona (2022, April 8) retrieved April 8, 2022 from

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