Genome complexity: new study on DNA repair (Introduction)

by David Turell , Monday, April 22, 2024, 17:59 (11 days ago) @ David Turell

Avoid making new telomeres:

https://www.the-scientist.com/keeping-telomeres-in-their-places-71791?utm_campaign=TS_N...

"Luckily, cells have developed a complex set of repair mechanisms to protect vulnerable DNA and fix damage so that the cell’s genomic instruction manual remains intact. Cells use homologous recombination to stitch double-stranded breaks (DSB) back together and the enzyme telomerase to cap exposed ends of a DNA strand with a repetitive DNA sequence called a telomere.

"However, if cells use the wrong repair mechanism for a given situation, it can be disastrous. For example, if telomerase tries to seal up a DSB, it can sever the chromosome, causing the cell to lose key genes. “The whole system falls apart,” said Titia de Lange, a cell biologist at Rockefeller University.

"Scientists have observed that this can happen in yeast and corn, but whether it occurred in humans remained a mystery until now. de Lange’s team has finally figured out just how rare this catastrophic event is in humans and how cells keep it in check. In a study published in Science, they revealed that while telomerase occasionally acts at DSB, the ataxia telangiectasia and Rad3-related (ATR) protein typically runs interference to give the cell a chance to repair these breaks.

***

"To figure out how the cells blocked telomerase from acting at DSB, de Lange’s team genetically inactivated many different enzymes and repair pathways to see if any of them repressed telomere formation. Eventually, they discovered the genomic guardian: ATR, a protein that senses DNA damage and triggers homologous recombination. When they inhibited ATR, the number of new telomeres nearly tripled.

***

"Much remains for de Lange and her team to reveal about ATR. Although they found that ATR represses telomerase, they don’t know how this happens. Arnoult said that she wonders whether there are other redundant pathways that can also influence telomere formation at DSB in other contexts. She pointed to other species where telomeres that form at DSB are a normal part of development.4,5 “Studying those species may give us clues of how they can do that very efficiently and why it's prevented in humans,” Arnoult said.

Comment: A view into how processes are controlled from making accidents. Making a telomere and thus putting an end on broken DNA at the wrong place destroys genes. ATR is the guiding force here. Now is a point to ponder. Did this defense develop because breaks happened early on, or was it designed from the beginning to avoid early loss of genes from brakes? Darwin-type unguided chance evolution could not have achieved this degree of controls. God's design of life requires this degree of freedom for active molecules creating a function. It must allow for mistake control. If this is how living biochemistry works, it must be the only way it can work.