Theodicy: fixing two-stranded DNA (Introduction)

by David Turell @, Tuesday, September 28, 2021, 14:44 (323 days ago) @ dhw

Bacteria do it easily and quickly:

"Both cables on a suspension bridge snap. It’s going to collapse. If repairmen cannot mend the cables extremely rapidly, the bridge is doomed, and all the cars on it will dump into the water. Time is of the essence. The task looks hopeless. What to do?

"Homologous Recombination
Cells face that kind of challenge every day, but they are well equipped to handle it. When both DNA strands break (the “double-stranded break” crisis, or DSB), a cell can die. Molecular machines fly into action as the strands flail about, threatening genomic catastrophe. The repair crew has an additional problem: unlike the bridge cable, the DNA strand is made up of a sequence of code that needs to match what was there before the DSB. In a process called homologous recombination, the machinery searches for a template to rebuild the broken sequence. Researchers at Uppsala University know that this process is mostly “well described in the literature.”

"However, the description usually disregards the daunting task of finding the matching template among all the other genome sequences. The chromosome is a complex structure with several million base pairs of genetic code and it is quite clear that simple diffusion in 3D would not be sufficiently fast by a long shot. But then, how is it done? This has been the mystery of homologous recombination for 50 years. From previous studies, it is clear that the molecule RecA is involved and important in the search process, but, up until now, this has been the limit of our understanding of this process. [Emphasis added.]

"Even a simple bacterium knows a trick to make the search easier. It reduces the search from a 3D problem to a 2D problem. With that shortcut, the cell reduces the time to repair down to 15 minutes on average. The Uppsala group, using CRISPR and fluorescent tags, watched the RecA proteins in real time. They published their findings in Nature.

“'We can see the formation of a thin, flexible structure that protrudes from the break site just after the DNA damage. Since the DNA ends are incorporated into this fiber, it is sufficient that any part of the filament findsthe precious template and thus the search is theoretically reduced from three to two dimensions. Our model suggests that this is the key to fast and successful homology repair,” says Arvid Gynnå, who has worked on the project throughout his PhD studies.

Original article:

"We further show that the search takes less than 9 ± 3 min (mean ± s.d) and is mediated by a thin, highly dynamic RecA filament that stretches throughout the cell. We propose that the architecture of the RecA filament effectively reduces search dimensionality. This model predicts a search time that is consistent with our measurement and is corroborated by the observation that the search time does not depend on the length of the cell or the amount of DNA. Given the abundance of RecA homologues5, we believe this model to be widely conserved across living organisms.


"Previous work has suggested that the repair of DSBs induced by I-SceI is carried out by ‘bundles’, which are complex structures formed by RecA10. These bundles are characterized by a thick central body, low mobility, tens-of-minutes lifetime, and are positioned between the nucleoid and the inner membrane. We have found that the RecA filaments involved in DSB repair are markedly different from these bundles: they are thin, dynamic, last only for minutes, and are present within the nucleoid (Fig. 3h, i). Notably, according to the reduced-dimensionality model, the search time is not affected by an increase in the amount of DNA, as long as the length of the filament scales with the amount of DNA. The mechanism therefore enables search in organisms with genomes larger than those of bacteria."

Comment: Since doubled-stranded DNA breaks kills cells, it is logical that this mechanism for repair was designed at the same time DNA was designed. Having both appear simultaneously by chance is not realistically possible. There must be a designer.

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