Genome complexity: handling replication errors (Introduction)

by David Turell , Thursday, January 19, 2017, 04:22 (2653 days ago) @ David Turell

Life cannot survive unless replication copy errors are quickly eliminated. The systems are in place:

http://casemed.case.edu/cwrumed360/news-releases/release.cfm?new"New research out of Case Western Reserve University School of Medicine describes a mechanism by which an essential quality control system in cells identifies and destroys faulty genetic material.

"In the new study, Baker and her team of researchers uncovered that ribosomes were stalled on mRNA at premature stop codons. This observation led to the discovery that one of proteins in the surveillance complex, UPF1, was important for interacting with the stalled ribosome and assisting with its release from the mRNA. The inability of UPF1 to properly communicate with the ribosome results in the failure of the mRNA to be targeted to rapid elimination and inactivates the whole surveillance system.
Moreover, Baker’s findings indicated that UPF1 harnesses energy found in adenosine triphosphate – a reserve for energy storage in the cell – to influence the function of the ribosome, and that this step in the cellular checkpoint is necessary for recognizing and destroying mRNA with premature stop codons."

http://www.nature.com/articles/ncomms14021

"Nonsense-mediated mRNA decay (NMD) represents a eukaryotic quality control pathway that recognizes and rapidly degrades transcripts harbouring nonsense mutations to limit accumulation of non-functional and potentially toxic truncated polypeptides. A critical component of the NMD machinery is UPF1, an RNA helicase whose ATPase activity is essential for NMD, but for which the precise function and site of action remain unclear. We provide evidence that ATP hydrolysis by UPF1 is required for efficient translation termination and ribosome release at a premature termination codon. UPF1 ATPase mutants accumulate 3′ RNA decay fragments harbouring a ribosome stalled during premature termination that impedes complete degradation of the mRNA. The ability of UPF1 to impinge on premature termination, moreover, requires ATP-binding, RNA-binding and NMD cofactors UPF2 and UPF3. Our results reveal that ATP hydrolysis by UPF1 modulates a functional interaction between the NMD machinery and terminating ribosomes necessary for targeting substrates to accelerated degradation."

http://www.pnas.org/content/early/2017/01/03/1615439114.short

"Cells must continuously repair inevitable DNA damage while avoiding the deleterious consequences of imprecise repair. Distinction between legitimate and illegitimate repair processes is thought to be achieved in part through differential recognition and processing of specific noncanonical DNA structures, although the mechanistic basis of discrimination remains poorly defined. Here, we show that Escherichia coli RecQ, a central DNA recombination and repair enzyme, exhibits differential processing of DNA substrates based on their geometry and structure. Through single-molecule and ensemble biophysical experiments, we elucidate how the conserved domain architecture of RecQ supports geometry-dependent shuttling and directed processing of recombination-intermediate [displacement loop (D-loop)] substrates. Our study shows that these activities together suppress illegitimate recombination in vivo, whereas unregulated duplex unwinding is detrimental for recombination precision. Based on these results, we propose a mechanism through which RecQ helicases achieve recombination precision and efficiency. "

Comment: Many more articles are presented in:

http://www.evolutionnews.org/2017/01/quality_control_3103426.html

Comment: There must be quality controls for all replication processes or life ceases. Further it must be present in the initial cells of life. Saltation by God.