A study of DNA replication targets genes for antibiotic resistance

A model for the initiation of SaPI DNA replication mediated by Rep.
A model for the initiation of SaPI DNA replication mediated by Rep. (a) ATP-independent flexibility of CTD reveals residues involved in iteron recognition. The diameter of the barrel may accommodate at its N- and C-terminal sides dsDNA. In (b), two hexamers speculatively depicted embracing dsDNA. Possible interactions between hexamers and hexamers may lead to opposite rotational motions that favor DNA distortion. Electrostatic DNA wrapping to the surface of the barrel (not pictured) may have been involved in the melting of ori. (C) The tilting motion of the CTD assists the drawer mechanism of the ATPase domain to unwind DNA and promote progression of the replication fork. Image: Qiao, Mir-Sanchis, et al.

Discovering how a specific type of protein moves DNA transcription could have implications for understanding how antibiotic resistance genes spread among bacteria, Swedish researchers said.

Studying DNA replication was a good starting point for identifying potential targets for future drug development, said Ignacio Mir-Sanches, principal investigator of the group at Umeå University that published the study.

Mir-Sanchi’s lab focuses on infection biology and studies disease Staphylococcus aureus bacteria. Researchers are interested in understanding the DNA replication of S. aureus bacteriaof viruses that infect S. aureus bacteria (called phages) and viral satellites. Viral satellites are viruses that parasitize other viruses.

S. aureus bacteria It infects and kills millions of people worldwide and is considered a major threat because bacteria have become resistant to almost all antibiotics. Interestingly, genes involved in antibiotic resistance are sometimes also found in viral satellites, which makes the work even more medically important. In recent years an increase in resistance S. aureus bacteria It has been observed in methicillin-resistant horses Staphylococcus aureus (MRSA) is a pathogen A major concern for veterinary researchers.

All cellular organisms must copy their genetic material, DNA, to reproduce, with one copy going to the daughter cell and the other copy going to the other daughter cell. A DNA molecule can be likened to a very long chain of beads, with the beads being the building blocks or units.

The beading thread has two strands intertwined to form a spiral structure, a double helix. To replicate its genetic material, a cell must pass one to two molecules of DNA, a process called DNA replication, and it begins with the separation of the two strands of DNA. To separate chains, cells have specialized proteins called helicases.

The research group at Umeå University’s Department of Medical Biochemistry and Biophysics has figured out how the vermin interact and move on DNA to separate its strands. This discovery was made possible by so-called cryoelectron microscopy, for which Umeå has one of the most advanced facilities in Sweden. This technique allows scientists to take snapshots of a single molecule. They can make a movie by combining millions of shots and seeing how helicopters move.

Cuncun Qiao, a postdoctoral researcher on the team and first author of the paper, said that when the footage was analyzed, they saw the helicopter move different parts, called spheres, through two separate motions. “Two spheres rotate and tilt toward each other. These motions give us clues about how these planes move on DNA and separate strands.”

The study, which is supported by the Wallenberg Center for Molecular Medicine (WCMM) in Umeå, is published in the scientific journal Nucleic acid research.

“The findings expand our understanding of how antibiotic resistance genes spread, although it is noteworthy that the movements we identified here were also seen in helicases in eukaryotic viruses and even in human cells,” Mir-Sanchez said.

“It’s always surprising how important mechanisms are preserved from phages to humans,” Mir-Sanchez said.

Self-loading choppers are coupled to the staphylococcal drawer mechanism with high inter-field flexibility. Cuncun Qiao, Gianluca Debiasi-Anders, and Ignacio Mir-Sanchis. Nucleic acid research50(14), 8349-8362. doi.org/10.1093/nar/gkac625

Leave a Comment