David's theory of evolution: God's error corrections III (Evolution)

by David Turell @, Wednesday, October 21, 2020, 20:53 (365 days ago) @ David Turell

Problems with DNA mistakes and whether they can be corrected:


"A team of Duke researchers has found that transcription factors have a tendency to bind strongly to "mismatched" sections of DNA, sections of the code that were not copied correctly. The strong binding of transcription factors to mismatched sections of regulatory DNA might be a way in which random mutations become a problem that leads to disease, including cancer.

"Most of the time, DNA replication in the body goes smoothly, with nucleotides locking arms with their complementary base pair and marching through the cycle together in intended A-T and C-G fashion. However, as Gordan describes it, "no polymerase is perfect" and every now and then, a nucleotide will be paired with the wrong partner, resulting in a mismatch.

"Pipetting transcription factor proteins on slides pre-blotted with thousands of DNA molecule samples, a research team led by Duke computational biologist Raluca Gordan Ph.D., showed that the proteins had a stronger bond with the sections of DNA with the mismatched base pairs than with those with perfectly matched base pairs, or "normal" DNA structure.

"But what makes these 'mistakes' an attractive binding site for transcription factor proteins? For insight, Gordan, an associate professor in the Department of Biostatistics and Bioinformatics and the Department of Computer Science, reached out to Hashim Al-Hashimi, Ph.D., a James B. Duke Professor of Biochemistry, and expert in DNA structure and dynamics who works just across the street.

"Al-Hashimi studies nucleic acids (DNA and RNA) and their interactions with proteins and small molecules, with the idea that how these biomolecules look and move is as important for their function as their chemical properties.


"'If we are ever to attain a deep and predictive understanding of how DNA is recognized by proteins in cells, we need to go beyond the conventional description in terms of static structures and move towards describing both DNA and the protein molecules that bind to them in terms of dynamic structures that have different preferences to adopt a wide range of shapes," Al-Hashimi said.

"Gordan said that going forward, the team hopes to understand how this interaction relates to disease development. If a mismatched base pair, bound strongly by a transcription factor, makes it through the DNA replication cycle without being repaired by another type of protein—known as a repair enzyme—it can become a mutation, and mutations can lead to genetic diseases like cancer and neurodegeneration. (my bold)

"'We are now convinced that the interactions between transcription factors and mismatches are really strong," she said. "So the next step is to understand what this means for the cell."

"We already know that regulatory regions of the genome harbor more cancer mutations than expected by chance. We just do not know why. The strong interactions between transcription factors and DNA mismatches, which could interfere with repair of the mismatches, provide a novel mechanism for the accumulation of mutations in regulatory DNA.'"

Comment: The mechanism described appears to make it easier to produce mutations. But note the bold. There are repair mechanisms present to reverse DNA mistakes and resist mutations.

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