https://phys.org/news/2022-08-enzyme-proteins-tidy-tail-dna.html

"Researchers at the University of Wisconsin–Madison have described the way an enzyme and proteins interact to maintain the protective caps, called telomeres, at the end of chromosomes, a new insight into how a human cell preserves the integrity of its DNA through repeated cell division.

"DNA replication is essential for perpetuating life as we know it, but many of the complexities of the process—how myriad biomolecules get where they need to go and interact over a series of intricately orchestrated steps—remain mysterious.

"'The mechanisms behind how this enzyme, called Polα-primase, works have been elusive for decades," says Ci Ji Lim, an assistant professor of biochemistry and principal investigator on new research into DNA replication published recently in Nature.

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"At the telomere construction site, Polα-primase first builds a short nucleic acid primer (called RNA) and then extends this primer with DNA (then called RNA-DNA primer). Scientists thought Polα-primase would need to alter its shape when it switches from RNA to DNA molecule synthesis. Lim's lab found that Polα-primase makes the RNA-DNA primer at telomeres using a rigid scaffold with the help of another cog in the telomere replication machine, an accessory protein called CST. CST acts like a stop-and-go sign that halts the activity of other enzymes and brings Polα-primase to the construction site.

"'Before this study, we had to imagine how Polα-primase works to complete telomere replication at the ends of chromosomes," says Lim. "Now, we have high-resolution structures of Polα-primase bound to an accessory protein complex called CST. We found that after CST binds to the template DNA strand at the telomere, it facilitates the action of Polα-primase. In doing so, CST sets the stage for Polα-primase to first synthesize RNA and then DNA using a unified architectural platform."

"'Because Polα-primase plays a central and very important role in DNA replication in telomeres and elsewhere along chromosomes—it's the only enzyme that makes primers on DNA templates from scratch for DNA replication—our CST–Polα-primase structure provides new insights into how Polα-primase can also do its job during genomic DNA replication," Lim says. "It's a very elegant solution that nature has evolved to accomplish this complicated process."

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"'Because Polα-primase plays a central and very important role in DNA replication in telomeres and elsewhere along chromosomes—it's the only enzyme that makes primers on DNA templates from scratch for DNA replication—our CST–Polα-primase structure provides new insights into how Polα-primase can also do its job during genomic DNA replication," Lim says. "It's a very elegant solution that nature has evolved to accomplish this complicated process."

"'Our findings reveal an unprecedented role that CST plays in facilitating this Polα-primase activity," explains first author Qixiang He, a graduate student in the UW–Madison biophysics graduate program. "It will be interesting to see if accessory factors involved in DNA replication elsewhere on chromosomes set up Polα-primase the same way as CST does for telomeres.'"

Comment: it is logical to imagine that a repair process was available when cell division first began. Without it early life might not have continued. Therefore, only design can be considered.