Genome complexity: DNA copying in short bursts (Introduction)

by David Turell , Monday, October 14, 2024, 17:52 (8 days ago) @ David Turell

The real way it happens:

https://www.the-scientist.com/dna-polymerase-works-in-short-bursts-rather-than-one-long...

"...suggesting that DNA replication and proofreading involves multiple polymerases. Now, in a publication in Nature Communications, a team at Vrije University Amsterdam provided additional evidence that DNA polymerase does not replicate DNA as continuously as once believed.

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"The researchers observed that, on average, a single DNA polymerase molecule remained bound to the nucleic acid at the junction for slightly more than one second—far from the continuous binding that most textbooks describe. Further contrasting from the dogma, during this time, a single enzyme only performed either extension or proofreading, occasionally also pausing on the DNA; rather than backing up to fix an error, the enzyme detached from the nucleic acid to let another bind.

“'The idea of having a motor that you put in reverse sounds very appealing to us, but it's much more efficient to throw the motor out,” Wuite explained. Unlike cars, a cell has multiple DNA polymerase motors, so an enzyme that is already in the configuration needed to bind the DNA and correct the error can take over. This exchange takes less energy than the same protein changing conformation to fulfill a different function.

"However, DNA polymerase’s activity appeared seamless and uniform, so the team considered that a process existed to help one enzyme pick up where another left off, acting like a memory. They analyzed one extension event and observed that polymerases unbound and rebound multiple times, but each time, they resumed the same function.

"To study this further, the team assessed the activity state—enzymatic or paused—before, during, and after a fluorescent polymerase bound the DNA over the course of several experiments. They found that the most common pattern was for the activity to be the same at all three observational points, whether the enzymatic period was during exonuclease repair or DNA extension.

“'This experiment is really the nail in the coffin of this model where everything is sitting stably on the DNA,” van Oijen said. He added that structural studies will be important for adding additional context to these mechanisms."

Comment: this adds much more complexity to the process of DNA copying with many more moving parts. Recognizing mistakes means the molecules carry a copy of what is expected as they read the new copy. As all of this is highly repetitive and exacting only design could produce it.