Genome complexity: early steps reproducing DNA (Introduction)

by David Turell @, Sunday, March 19, 2017, 23:38 (2592 days ago) @ David Turell

As usual very complex right formation:

https://phys.org/news/2017-03-human-dna-replication-captured-atomic.html

"The process is so complex, calling for the orchestration of over a hundred highly specialized proteins, each of which must play its part at precisely the right moment and in the proper spatial orientation. It has often been compared to an exquisitely choreographed molecular dance. The smallest errors, left uncorrected, can have deadly consequences

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"The images of the human version of this complex, called ORC - for origin recognition complex - show it in its active mode.

"ORC complexes self-assemble in the cell nucleus and bind at specific spots called start sites or origins along the double helix in chromosomes. In human cells, ORC assembles at literally thousands of origin sites across the entire genome, to form an initial configuration called the pre-replication complex, or pre-RC. Once assembled, these pre-RCs are like highly prepared Olympic swimmers standing on the starting block, waiting for the signal to start the race.

"Like fast swimmers, each complex needs fuel to recruit its "motor" that opens the two strands of the double helix. In the case of ORC it is ATP, or adenosine triphosphate. In ORC's active phase, the researchers showed that a subassembly containing ORC subunits 1,2,3,4 and 5 engages multiple ATP molecules and forms a partial ring-shaped complex. ATP is also used to recruit another protein component called CDC6, transforming the open ring into a closed ring. By this time, the multi-part assembly has engaged and bound to the double helix, which passes through the center of the ring like a bolt through the center of a nut. The ring is designed to fit the DNA snugly.

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"Although ORC in primitive yeast and complex human beings operates differently - the yeast protein is stable during cell division while in humans it is dynamically assembled and taken apart - they are "remarkably similar" in important respects, the researchers note.

"'Both are highly similar to another ATP-driven machine that also loads a ring-shaped protein onto DNA, the DNA polymerase clamp-loaders, showing that these molecular machines that load ring-shaped proteins onto DNA have been re-purposed for multiple stages of DNA replication," the team writes. They both act as molecular switches that hydrolyze the energy of ATP to lock protein rings on double strand DNA. "

Comment: More understanding of the complexity involved. There is no way to develop this process stepwise without inviting fatal errors. Only saltation fits originating this process.


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