Genome complexity: cell splirtting DNA mechanics (Introduction)

by David Turell , Thursday, February 25, 2016, 13:50 (3195 days ago) @ David Turell

Cells reproduce constantly by splitting in two. This requires unzipping DNA and making duplicate strands. The molecular machine that does this is called a helicase, and it walks along the DNA and rocks back and forth splitting. And it is and extremely complicated structure:-http://www.evolutionnews.org/2016/02/is_it_a_pumpjac102625.html-"One part binds and releases energy from a molecule called ATP. It converts the chemical energy into a mechanical force that changes the shape of the helicase," Li said. After kicking out the spent ATP, the helicase complex goes back to its original shape so a new ATP molecule can come in and start the process again.-"It looks and operates similar to an old style pumpjack oil rig, with one part of the protein complex forming a stable platform, and another part rocking back and forth," Li said. Each rocking motion could nudge the DNA strands apart and move the helicase along the double helix in a linear fashion, he suggested-The source article: -http://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.3170.html-(Look at the diagrams. Complex!)-Abstract: -"The CMG helicase is composed of Cdc45, Mcm2-7 and GINS. Here we report the structure of the Saccharomyces cerevisiae CMG, determined by cryo-EM at a resolution of 3.7-4.8 Å. The structure reveals that GINS and Cdc45 scaffold the N tier of the helicase while enabling motion of the AAA+ C tier. CMG exists in two alternating conformations, compact and extended, thus suggesting that the helicase moves like an inchworm. The N-terminal regions of Mcm2-7, braced by Cdc45-GINS, form a rigid platform upon which the AAA+ C domains make longitudinal motions, nodding up and down like an oil-rig pumpjack attached to a stable platform. The Mcm ring is remodeled in CMG relative to the inactive Mcm2-7 double hexamer. The Mcm5 winged-helix domain is inserted into the central channel, thus blocking entry of double-stranded DNA and supporting a steric-exclusion DNA-unwinding model.-***-"DNA replication is a major source of errors that can lead to cancer," explained Li, a Professor in the Department of Biochemistry & Cell Biology at Stony Brook University, a scientist at Brookhaven Lab, and lead author of the paper. "The entire genome -- all 46 chromosomes -- gets replicated every few hours in dividing human cells," Li said, "so studying the details of how this process works may help us understand how errors occur. -***-"Yet the machinery is much more rapid than the best typist. It rocks! -- not like the slow, lumbering mechanism of the oil pumpjack, but at blinding speed. Jonathan M. wrote here at Evolution News that DNA replication works at 749 bases per second with an error rate of 10-7 to 10-8. Yet the cell performs this feat in just hours, trillions of times in your body. Nor does it work alone. All the other machines in the DNA replication factory keep up with it, bringing in nucleotides, proofreading them, and fastening the new helices together."-Comment: Just one 'simple' part of how living things thrive. Not by chance!