Genome complexity: DNA repair mechanisms (Introduction)

by David Turell , Monday, October 07, 2024, 21:18 (15 days ago) @ David Turell

A new one described:

https://www.sciencedaily.com/releases/2024/10/241004121853.htm

"DNA damage response, or DDR for short, is the technical term for this. Specific signaling pathways usually initiate the immediate recognition and repair of DNA damage, thus ensuring the survival of the cell.

***

"The group has identified a new mechanism of the DNA damage response that is mediated via an RNA transcript. Their results help to broaden the conceptual view on the DNA damage response and to link it more closely with RNA metabolism.

***

"'In our study, we focused on so-called long non-coding RNA transcripts. Previous data suggest that some of these transcripts act as regulators of genome stability," says Kaspar Burger, explaining the background to the work. The study focused on the nuclear enriched abundant transcript 1 -- also known as NEAT1 -- which is found in high concentrations in many tumor cells. NEAT1 is also known to react to DNA damage and to cellular stress. However, its exact role in the DNA damage response was previously unclear.

"'Our hypothesis was that RNA metabolism involves NEAT1 in the DNA damage response in order to ensure the stability of the genome," says Burger. To test this hypothesis, the research group experimentally investigated how NEAT1 reacts to serious damage to the genome -- so-called DNA double-strand breaks -- in human bone cancer cells. The result: "We were able to show that DNA double-strand breaks increase both the number of NEAT1 transcripts and the amount of N6-methyladenosine marks on NEAT1," says the scientist.

***

"The experiments conducted by Kaspar Burger and his team show that the frequent occurrence of DNA double-strand breaks causes excessive methylation of NEAT1, which leads to changes in the NEAT1 secondary structure. As a result, highly methylated NEAT1 accumulates at some of these lesions to drive the recognition of broken DNA. In turn, experimentally induced suppression of NEAT1 levels delayed the DNA damage response, resulting in increased amounts of DNA damage.

"NEAT1 itself does not repair DNA damage. However, as the Würzburg team discovered, it enables the controlled release and activation of an RNA-binding DNA repair factor. In this way, the cell can recognize and repair DNA damage highly efficiently."

Comment: another very precise mechanism to aid in DNA repair. In separating chromosomes during cell splitting forces are acting and can cause tears. This is unlike a mistake in folding, thus another form of mistake as is the joining improperly of molecules. Living mistakes are or was the result of all these free-floating actions, upon which operational life begins.