INCARNATE

Rocks don’t care if they break. The very concepts of proofreading and repair imply accuracy for a purpose. In cells, complex multi-part machines find errors and fix them. Is this not evidence of intentionality and programming? As these new research papers show, the machines involved show exquisite craftsmanship and efficient action to keep other parts — machines outside their own structural needs — humming along. 

How can they do that? How do they know? They bear an uncanny resemblance to surgeons or linemen that are trained as first responders to potentially catastrophic situations, and yet they work robotically in the dark without eyes or brains. Such things do not just appear by blind material processes. Proofreading and repair systems had to be operational from the beginning of life, because considering the lethal consequences without them, it’s hard to conceive of any primitive organism surviving, let alone progressing up an evolutionary ladder. Now, behold in wonder what is going on in our cells.

Stop and Reel

Before cells divide, billions of DNA base pairs must be precisely duplicated. About one time in 10 million, a wrong base is inserted into the copy. Researchers at North Carolina State University found “genome guardians” that “stop and reel in DNA” during this important operation. Two enzymes cooperate to proofread the copy. They halt the duplication when a mismatch is found until more machines can fix the error. 

A pair of proteins known as MutS and MutL work together to initiate repair of these mismatches. MutS slides along the newly created side of the DNA strand after it’s replicated, proofreading it. When it finds a mismatch, it locks into place at the site of the error and recruits MutL to come and join it. MutL marks the newly formed DNA strand as defective and signals a different protein to gobble up the portion of the DNA containing the error. Then the nucleotide matching starts over, filling the gap again. The entire process reduces replication errors around a thousand-fold, serving as one of our body’s best defenses against genetic mutations that can lead to cancer. [Emphasis added.]

Well, is that not a tragedy for Darwin? Evolutionists need those mutations to build eyes and wings!

Repair Squads

When cells divide, double-stranded breaks can occur. These are particularly dangerous, often associated with cancer. Medical researchers at University of Texas Health in San Antonio confirm that DNA repair requires multiple tools. Drs. Daley, Sung, and Burma at UT knew that the repair operation, called homologous recombination, is done by resection enzymes, but they were curious why so many different enzymes were involved. Why does the cell “need three or four different enzymes that seem to accomplish the same task in repairing double-strand breaks”? The “perceived redundancy,” they concluded, “is really a very naïve notion.” Like a skilled workman, the cell maintains “An array of tools, each one finely tuned.”

“It’s like an engine mechanic who has a set of tools at his disposal,” Dr. Sung said. “The tool he uses depends on the issue that needs to be repaired. In like fashion, each DNA repair tool in our cells is designed to repair a distinctive type of break in our DNA.”

Surgical Team

Another type of error can occur when a gene is being transcribed. If RNA polymerase (RNAP, the transcribing machine) hits a lesion caused by UV radiation or some other mutagen, the transcription can stall. Thankfully, there is a programmed response called transcription-coupled nucleotide excision repair (TC-NER) that knows what to do. That’s a good thing, because faulty repair can lead to “the severe neurological disorder Cockayne syndrome,” characterized by microcephaly, delayed development, short stature, low weight gain, and numerous other problems like oversensitivity to sunlight, “hearing loss, vision loss, severe tooth decay, bone abnormalities, hands and feet that are cold all the time, and changes in the brain that can be seen on brain scans” (Genetics Home Reference). 

Four researchers from Washington University, publishing in PNAS¹, learned more about the poorly understood process of TC-NER, and revealed a plethora of molecular machines and factors involved. “The initiation of TC-NER upon RNAP stalling requires specific factors,” they begin. “These factors respond rapidly to transcription-blocking DNA damage, binding to stalled RNAP to coordinate assembly of downstream NER factors.” Moreover, the repair program must be able to handle a variety of situations. The technical details are too inscrutable for most readers to describe here (and this was about research on yeast!); suffice it to say that TC-NER is a well-choreographed, irreducibly complex process that, fortunately, works most of the time. Children with Type 2 Cockayne Syndrome may only live up to age 7 (NIH). 

Preventive Repair

The cell has mechanisms for preventing errors, too. Research at Mt. Sinai Medical Center in New York City “has unraveled for the first time the three-dimensional structure and mechanism of a complex enzyme that protects cells from constant DNA damage, opening the door to discovery of new therapeutics for the treatment of chemotherapy-resistant cancers.” They used cryo-electron microscopy to study DNA polymerase ζ at a near-atomic level. This important enzyme’s “architecture and mechanism have been a mystery to scientists for years.” Could any primitive life-form get by without something like this?

DNA polymerase ζ is the crucial enzyme that allows cells to battle the more than 100,000 DNA-damaging events that occur daily from normal metabolic activities and environmental intrusions like ultraviolet light, ionizing radiation, and industrial carcinogens. The Mount Sinai team, which included first author Radhika Malik, PhD, Assistant Professor of Pharmacological Sciences, learned how the enzyme protects the cells from natural and manmade environmental as well cellular stresses through an intricate structure of four different proteins that connect to each other in a pentameric, or daisy chain-like, configuration.

Didn’t the Darwinians tell us that UV light and ionizing radiation were sources of the “building blocks of life” and the mutations that nature can select to build humans from bacteria? No way. These findings are published in Nature Structural & Molecular Biology². 

Genetic Bouncers 

DNA bases on opposite strands connect via hydrogen bonds, but sometimes a protein interloper makes a bogus connection. “Covalent cross-links between proteins and DNA are among the most hazardous types of DNA damage,” says the Ludwig-Maximilian University of Munich. Fortunately (again), there’s an app for that.

Chemical lesions in the genetic material DNA can have catastrophic consequences for cells, and even for the organism concerned. This explains why the efficient identification and rapid repair of DNA damage is vital for survival. DNA-protein crosslinks (DPCs), which are formed when proteins are adventitiously attached to DNA, are particularly harmful. DPCs are removed by the action of a dedicated enzyme — the protease SPRTN — which cleaves the bond between the protein and the DNA.

DPCs can occur during natural metabolism or by contact with synthetic chemicals. SPRTN has a challenging job, they say, because it must be able to tackle a variety of situations; “the enzyme has to be able to identify many different structures as aberrant.” Its two domains must engage for it to recognize the error and fix it. Julian Stingele explains this fail-safe system:

One binds to double-stranded, and the other to single-stranded DNA. “So the protein uses a modular system for substrate recognition. Only when both domains are engaged is the enzyme active — and DNA in which double-stranded and single-stranded regions occur in close proximity is often found in the vicinity of crosslinks,” says Stingele.

When this system isn’t working properly, patients are subject to liver cancer and early aging.

An Act of Mind

We have just looked at five different types of errors that are repaired by five different systems of molecular machines. Each system must first recognize the error and then know what to do; otherwise, the consequences can be catastrophic. In each case, the machinery is well designed and finely tuned to solve the problem, and it does so rapidly and efficiently. That takes foresight, and foresight implies intelligent design. As Marcos Eberlin says in his book Foresight: How the Chemistry of Life Reveals Planning and Purpose, “This act of anticipation — foresight — is not a characteristic of blind material processes. It is an act of intelligence, of a mind” (p. 81).

Notes

1. Duan et al., “Genome-wide role of Rad26 in promoting transcription-coupled nucleotide excision repair in yeast chromatin.” PNAS August 4, 2020 117 (31) 18608-18616. https://doi.org/10.1073/pnas.2003868117
2. Malik et al., “Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis.” Nature Structural & Molecular Biology, 17 August 2020. https://doi.org/10.1038/s41594-020-0476-7

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I will give thanks to You, for I am fearfully and wonderfully made;
Wonderful are Your works,
And my soul knows it very well. Psm. 139:14

“God loves you and I love you that’s the way it’s gonna be!” – Mike

JAMES B. LONGLEY, who would one day become the governor the Maine was selected by his peers as one of the outstanding members of his college class…

At the conclusion of his graduate ceremony, Longley’s mother took him aside and gave him a piece of sobering advice.

She said, “Jim, I was very proud of you today, and I think you will win many honors in your life.

But keep this in mind – despite the honors, there’s one circumstance more than any other that will determine the turnout at your funeral. . .and that will be…the weather…”

THOUGHT: Sometimes we need to be reminded that we’re not quite as grand as we would have ourselves to believe.

“For I say through the grace given to me, to everyone who is among you, not to think of himself more highly than he ought to think, but to think soberly. . .” (Rom. 12:3a).

“God loves you and I love you and that’s the way it’s gonna be!” – Mike