Genome complexity: DNA repair at molecular level (Introduction)

by David Turell , Monday, March 21, 2022, 19:07 (768 days ago) @ David Turell

A different explanation than the original article in a second study:

https://www.sciencedaily.com/releases/2022/03/220321132210.htm

"The fact [is] that our DNA requires constant upkeep to maintain its integrity. Were it not for dedicated DNA repair machinery that routinely fixes mistakes, the information within DNA would be rapidly degraded.

"This repair happens at cell cycle checkpoints that are activated in response to DNA damage. Like a quality assurance agent on an assembly line, proteins that participate in the DNA damage checkpoint assess the cell's DNA for mistakes and, if necessary, pause cell division and make repairs. When this checkpoint breaks down -- which can happen as a result of genetic mutations -- DNA damage builds up, and the result is often cancer.

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"As a result of this effort, his lab has purified several components of the repair machinery, including 9-1-1 proteins and proteins that facilitate the binding of 9-1-1 to DNA.

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"Much like the gears and levers of a machine, it's these movements of amino acids that allow proteins to serve as the workhorses of the cell, including those that repair DNA.

"'Using cryo-EM, we're able to not only determine one structure but an ensemble of structures. By putting these structures together in a logical pattern, based on the new data and previous biochemical data, we can come up with a proposal for how this clamp works."

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"Much like the gears and levers of a machine, it's these movements of amino acids that allow proteins to serve as the workhorses of the cell, including those that repair DNA.

"'When Dirk came to us, we realized that many of the tools that our lab has developed over the past few years were perfectly suited to answering this question," Dr. Hite says. "Using cryo-EM, we're able to not only determine one structure but an ensemble of structures. By putting these structures together in a logical pattern, based on the new data and previous biochemical data, we can come up with a proposal for how this clamp works."

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"'It had been thought from all studies prior to this that clamps would open in the manner of lock washer, where basically the two open ends of the clamp would rotate out of plane to create a narrow gap," Dr. Remus says. "But what Rich observed is that the 9-1-1 clamp opens much more widely than anticipated, and it opens completely in plane -- there's no twisting like in the lock-washer scenario."

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"Another surprise was that the 9-1-1 clamp loader complex was observed to bind DNA in the opposite orientation from other clamp loader complexes that act on undamaged DNA during normal DNA replication. This observation explained how 9-1-1 is specifically recruited to sites of DNA damage."

Comment: this repair mechanism had to have been designed when DNA code was first designed. The possibility of breaks was recognized and protected against. There would be no DNA- dependent life surviving without it. Basically, you can't have one without the other. Necessarily inseparable.