Genome complexity: cell splitting DNA controls (Introduction)

by David Turell @, Monday, May 09, 2022, 23:52 (689 days ago) @ David Turell

An interplay of enzymes:

https://phys.org/news/2022-05-crystal-dna-mystery.html

"When cells reproduce, the internal mechanisms that copy DNA get it right nearly every time. Rice University bioscientists have uncovered a tiny detail that helps understand how the process could go wrong.

"Their study of enzymes revealed the presence of a central metal ion critical to DNA replication also appears to be implicated in misincorporation, the faulty ordering of nucleotides on new strands.

***

"Rice structural biologist Yang Gao, graduate student Caleb Chang and alumna Christie Lee Luo used time-resolved crystallography to analyze the flexible enzymes called polymerase as they bend and twist to rapidly reassemble complete strands of DNA from a pool of C, G, A and T nucleotides.

"All of the proteins involved in DNA replication rely on metal ions—either magnesium or manganese—to catalyze the transfer of nucleotides to their proper positions along the strand, but whether there were two or three ions involved has long been a topic of debate.

"The Rice team seems to have settled that through studying a polymerase known as eta, a translesion synthesis enzyme that guards against ultraviolet-induced lesions.

***

"Gao said typical polymerases resemble a right-handed shape, and he thinks of them in terms of an actual hand: "They have a palm domain that holds the active site, a finger domain that closes up to interact with the new base pair, and a thumb domain that binds the primer/template DNA," he said.

***

"The study led to their theory that the first of the three metal atoms in eta supports nucleotide binding, and the second is the key to keeping the nucleotide and primer on track by stabilizing the binding of loose nucleotides to the primer located on the existing half of the new strand (aka the substrate). Primers are short DNA strands that mark where polymerases start stringing new nucleotides.

"'Only when the first two metal ions are in check can the third one come and drive the reaction home," said Chang, suggesting the process may be universal among polymerases.

"The researchers also noted poly-eta contains a motif that makes it prone to misalignment of primers, leading to a greater chance of misincorporation.

"'This is, first, about a basic mechanism of life," Gao said. "DNA has to be copied accurately, and errors can lead to human disease. People who study these enzymes know that for DNA synthesis, they always do much, much better than they should because there's a very limited amount of energy available for them to choose the right base pair.'"

Comment: cell division is an ancient process going back to the first dividing cell divisions. The enzymes involved are giant exactly designed molecules. All of this mechanism has to be designed together at the same time. There is no way stepwise chance mutations could create such arrangement. It is irreducibly complex and must be formed by a designer, at the start of life's first cells.


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