Immune complexity: pacing DN A and repairing it (Introduction)

by David Turell @, Friday, February 26, 2021, 05:10 (1126 days ago) @ David Turell

All done by molecular motors:

https://www.nature.com/articles/d41586-021-00351-1?WT.ec_id=NATURE-20210225&utm_sou...

"Cells neatly compact their spaghetti of DNA in several ways. In cells with a nucleus, the DNA is first wrapped around cores of histone proteins to make structures called nucleosomes, which together form a chromatin fibre that looks like beads on a string. Loop extrusion is the subsequent compaction process, whereby a molecular motor binds a chromatin fibre and reels it in from the sides, forcing out a progressively larger loop in between.

"Although the process of loop extrusion was hypothesized decades ago, only in the past few years has it become clear that it is a universal mechanism that organizes DNA in organisms from bacteria to humans. In 2016, computational models showed that extrusion can compact DNA, turning a hairball of chromatin into detangled yet tightly packed chromosomes. Simulations also indicated that, when extrusion is stalled by barriers on the chromatin (a normal part of the process), it produces chromosomal domains seen in data from Hi-C — a technique used to characterize chromosome structure.

"These studies further suggested that ‘structural maintenance of chromosomes’ (SMC) complexes — once thought to be passive rings or staples — are actually loop-extruding motors. Moreover, proteins known as CCCTC-binding factors (CTCFs), which attach to specific DNA sequences, were proposed to be barriers that catch and stall SMC motors called cohesins (Fig. 1b). All in all, a range of experimental evidence — from in vivo depletion of SMCs and CTCFs, to direct visualization of single molecules — now supports the existence of loop extrusion8.

***

"Arnould et al. add to this list of possibilities, suggesting that loop extrusion safeguards the genome by supporting the repair of double-strand DNA breaks (DSBs).

"To repair severed DNA, cells must first establish a large (roughly one million base pair) region of modified H2AX histones flanking the break. Phosphate groups are added to the histones by certain enzymes, including one called ATM, producing a region of what are known as γH2AX histones. These histones signal the presence of the break to repair enzymes."

Comment: These motorized molecules are amazing. The excerpts are just a hint of the complexity described in this article, much of which is offering probabilities of h ow it all works at a molecular level. See the diagrams to help in understanding the findings. A marvelous example of the need to recognize a designer is necessary,


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