Genome complexity: more findings on DNA repair (Introduction)

by David Turell , Wednesday, March 30, 2022, 18:51 (968 days ago) @ David Turell

More complex than ever:

https://phys.org/news/2022-03-global-dna.html

"Widely accepted work, including studies that led to a 2015 Noble Prize, had argued that TCR played a relatively small role in repair because it relied on a putative TCR factor that made only a marginal contribution to DNA repair. A parallel process, global genome repair (GGR), was assumed to scan and fix most of DNA independent of transcription. Both processes were thought to set the stage for nucleotide excision repair (NER), in which a damaged stretch of DNA was snipped out and replaced by an accurate copy.

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"Contrary to the conventional dogma, the study found that RNA polymerase serves as the scaffold for the assembly of the entire NER complex, and as the primary sensor of DNA lesions. It turned out that the principal NER enzymes UvrA and UvrB do not locate most lesions on their own, but are delivered to them by RNA polymerase. This fundamental TCR process is independent of Mfd, say the authors.

"The second study, published in Nature Communications, again in living cells, used a high-throughput sequencing technology called CPD-seq to track the appearance of DNA lesions upon exposure to UV light, and the rate of repair with a resolution down to a single letter (nucleotide) in the DNA code. CPD-seq showed that interfering with bacterial transcription using the antibiotic rifampicin shuts down repair throughout the bacterial genome. The study findings argue that NER is tightly coupled to transcription everywhere in the bacterial chromosome, the DNA infrastructure that houses all the genes.

"In another fascinating leap, experiments showed that bacterial cells, in the face of DNA damage, inhibit the action of the protein Rho, the global termination signal which tells RNA polymerase to stop reading. With the stop signals dialed down, RNA polymerases read on and on, delivering the repair enzymes to DNA damage anywhere it was encountered throughout the genome.

"'Given our findings, we theorize that eukaryotes, including human cells, also use RNA polymerase for efficient repair globally, as the bacterial TCR complexes described here have human analogs," says co-first author of the Nature study Binod Bharati, Ph.D., a post-doctoral scholar in Nudler's lab. "Moving forward, our team plans to confirm the presence of global TCR in human cells, and if confirmed, to explore whether in the future repair might be safely boosted to counter diseases of aging.'"

Comment: this is an irreducibly complex repair mechanism that had to be designed when DNA was designed. since broken DNA means life cannot continue. How much design in living biology is needed before the existence of the designer is accepted???