Enzyme and Proteins Work Together to Maintain the Telomeres, at the End of Chromosomes

Many of the complexities of DNA replication remains unknown. These include how countless biomolecules reach their locations and interact across several highly coordinated steps.DNA

Mammalian DNA polymerase-alpha/primase (pol-/primase) is required for DNA metabolism because it provides the de novo RNA-DNA primer for numerous DNA replication pathways. The pathways include lagging-strand synthesis and telomere C-strand fill-in. The fundamental physical mechanism by which pol-primase executes its complex multistep primer synthesis activity, either alone or in collaboration with accessory proteins, remains unknown.

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Study researchers have examined the interaction of an enzyme and proteins to maintain telomeres. Telomeres are the protective caps at the end of chromosomes.

This provides new insight into how a human cell maintains the integrity of its DNA through repeated cell division.

The current study shows that CST, a pol-primase accessory protein complex that binds single-stranded DNA, physically prepares the enzyme for effective primer production.

Significant progress in DNA synthesis

For decades, scientists have been trying to figure out how this enzyme, known as Pol-primase, operates. The discovery makes significant advances in understanding DNA synthesis at the ends of chromosomes and new assumptions about how Pol-primase—a key cog in the DNA replication machine—works.

The telomeres at the ends of the long DNA molecules that make up a single chromosome shorten significantly each time a cell divides. Telomeres safeguard chromosomes in the same way an aglet protects the end of a shoelace. Eventually, the telomeres become so short that crucial genetic code on a chromosome is exposed, and the cell enters a death condition, unable to operate normally. Preventing excessive shortening of DNA by refilling it with Pol-primase is part of a cell’s regular maintenance.

Pol-primase first constructs a short nucleic acid primer ( RNA) at the telomere building site, then expands this primer with DNA (then called RNA-DNA primer). Scientists hypothesized that Pol-primase would need to change structure while switching from RNA to DNA molecule creation.

The study shows that Pol-primase constructs the RNA-DNA primer at telomeres utilizing a stiff scaffold with the assistance of another cog in the telomere replication machine, an accessory protein termed CST.

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CST functions as a stop sign, halting the action of other enzymes and bringing Pol-primase to the construction site.

The researchers created the structural model of CST-Pol-primase by utilizing cryo-electron microscopy single-particle analysis, a sophisticated imaging technique.

Pol-primase is the sole enzyme that creates primers on DNA templates from the beginning for DNA replication at telomeres and elsewhere along chromosomes. The CST-Pol-primase structure provides fresh insights into how Pol-primase can also execute its work during genomic DNA replication.

Clinical significance

DNA is a vital part of life and science. Understanding the exact nature of its replication is necessary to develop artificial models of DNA structures. The study helps explain the role of proteins and enzymes in DNA replication. These findings can help in the development of new drugs with a better mechanism of action.

Conclusion

The novel discovery of the CST protein structure gives a new perspective to DNA science. The study creates a groundwork for further studies on the role of a protein and enzyme uniformed approach for an explanation of DNA replication.

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References

Structures of the human CST-Polα–primase complex bound to telomere templates

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