DNA read replication research is progressing, and it is expected to find a treatment plan for genetic diseases
By in-depth analysis of how the various components of DNA (DNA) are spliced ​​together, two groups of scientists have revealed how DNA formats and preserves genetic information.
New research shows people the unexpected changes in DNA programming.
To "turn on" and "turn off" the genes on the DNA, the enzymes in the cell must interact with the nucleosome; the nucleosome is a protein-containing complex that helps the cell complete the DNA arrangement.
Among these enzymes, one is called Dot1L, and its mutation is associated with childhood leukemia.
To assist in the recruitment of Dot1L, a small molecular protein marker called ubiquitin must first be attached to the nucleosome.
However, how the Dot1L enzyme physically binds nucleosomes or ubiquitin markers has been a mystery. Today, in the first study, Cynthia, Professor of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, USA. Wolberger and his laboratory postdoctoral Evan Worden finally solved the mystery.
The researchers used a cryo-electron microscopy (cryo-EM) imaging tool to freeze the molecules in the nucleosome and Dot1L to study how they interact.
In a new study published in the journal Cell recently, they found unexpected results: Dot1L changes the shape of the nucleosome and binds it more tightly with the Dot1L enzyme.
The high-resolution images taken with cryo-EM reveal a major change that has never been seen in the center of the nucleosome. When Dot1L is connected, the tail structure protruding from the center of the nucleosome oscillates upward, and the enzyme is fixed to the surface of the nucleosome, causing a series of other changes in the nucleosome structure.
The researchers say that this observation will change the way people think about genetic diseases, because changes in nucleosome structure affect how cells acquire DNA. Worden said: "This is a new entry point, and even makes us unexpected new discoveries."
Understanding how nucleosomes bind to Dot1L by changing shape can help scientists find new treatments that target this connection, especially in the treatment of childhood leukemia.
In another study, scientists focused on a process that trillions of times occurred throughout the human body: a miniature "molecular machine" that copies a DNA molecule in a cell into two, or exactly 60 without errors. Copying of hundreds of DNA fragments.
“This kind of precision is incredible, and it is in such a microscopic situation,†said James Berger, director of the American Institute of Basic Biomedical Sciences.
The term "replica" is used by scientists to refer to molecular machines that replicate DNA. The replicator consists of a series of proteins and enzymes that combine to form a DNA replicator.
Berger said: "We have learned how the various components of the replica work, but we don't know how they work together."
The researchers pointed out that the replica is like a self-contained copy machine that can copy a DNA fragment into two.
The "engine" that drives this copying machine is the helicase. The helicase unwinds the pairing and helix of the DNA duplex, allowing the copyer to acquire and replicate the molecular information stored in the form of a genetic code.
Like many car engines, helicase is driven by six "cylinders" or "rings" that can wrap around DNA and move along its threads.
Berger's team used bacteria as a research object to discover how the DnaC enzyme binds the helicase loop to DNA.
In a recent report in the journal Molecular Cell, scientists found that DnaC binds to helicase with one of its six-armed structures, allowing the helicase loop to loosen, open it, and attach it to the DNA strand. At this point, DnaC completes the task.
Today, Berger's lab continues to study how DnaC departs from the replicator complex, how the helicase "engine" locks the replicator complex, and how the helicase moves along the DNA.
Their findings will lay the groundwork for determining the helicase targets for antibacterial therapy in order to gain insight into the genetic diseases caused by the error mutations in the helicase.
Source: Chinese Journal of Science
Dental sealing machine,sealing machin dental
Foshan Ja Suo Medical Device Co., LTD , https://www.fjoralinstrument.com