Scientists discover the mechanism for the formation of high-order DNA structures

For the first time, molecular biologists have pointed out how one specific process uses energy to ensure the histone is properly placed on DNA to form chromatin. Their findings were published on Dec. 17 in Nature Communications.

The learning absorbed on the proteins called histone chaperones. Histone chaperones are accountable for adding and eliminating specific histones at specific times during the DNA packaging procedure. Misregulation of the expression of genes or aberrant duplication of DNA at the wrong time and place may result from the wrong histone. Therefore, histone chaperones are key players in the assembly and disassembly of chromatin.

“To carefully control the assembly and disassembly of chromatin units, histone chaperones act as molecular escorts to prevent the aggregation of histones and unwanted interactions,” said Professor Ji-Joon Song of the KAIST Department of Biological Sciences. “We established available to understand how chemical energy is used by a unique histone chaperone to gather or disassemble chromatin.” Song and his team looked to Abo1, the only known histone chaperone that uses cellular energy (ATP). While Abo1 is found in yeast, in other organisms, comprising humans, it has a similar partner called ATAD2.

Both use ATP, which is generated by a mechanism in which enzymes break down the phosphate bond of a molecule. Normally, ATP energy is used to fuel other cellular processes, but for histone chaperones, it is a special friend.

“This was an stimulating dispute in the field because all other histone chaperones that have continuous verified so far do not use ATP,” said Song. The scientists will evaluate the protein suggestions at the single-molecule level by imaging Abo1 with a single-molecule fluorescence imaging technique known as the DNA curtain test.

The method allows scientists to organize the molecules and proteins of DNA on a single layer of a microfluidic chamber and analyze the layer using microscopy of fluorescence.

The researchers found that Abo1 is ring-shaped and changes its structure to accommodate and deposit a specific histone on DNA by means of real-time observation. In fact, they find that ADP powered the welcoming structural changes.

“We detection a appliance by which Abo1 accommodates histone substrates, ultimately permitting it to act as a unusual energy-dependent histone chaperone,” said Song. “We also establish that despite the arrival of a protein disassembly machine, Abo1 actually loads histone substrates onto DNA to facilitate the assembly of chromatin.” Researchers plan to continue to explore how energy-dependent histone chaperones bind and release histones, with the ultimate goal of developing therapies that can target cancer-causing misconduct through the analogous human counterpart of Abo1.