Tiny Loops in Dividing Cells: Re-thinking 3D Genome Architecture

    A recent study by researchers at the Massachusetts Institute of Technology revealed the existence of tiny chromatin loops (aka micro-compartments) in the genomes of dividing cells. This finding challenges the longstanding belief that the 3D structure of the genome largely disassembles during mitosis. For those of us studying genetics, this is significant because gene expression and regulation are deeply influenced by how chromosomes fold in three-dimensional space. Interactions between enhancers and promoters, as well as the formation of loops, help determine when genes are turned on or off. If dividing cells maintain more of that 3D structure than we once believed, it could change the way we one thought cells restart their gene activity after they divide, because parts of the 3D structure might already be in place instead of having to rebuild everything. It also suggests that daughter cells might inherit not just DNA, but some of the physical “layout” that helps control which genes are on or off. And if that structure is important, then mistakes in how the genome folds during division could play a bigger role in causing diseases like cancer.

    These findings also raise several interesting questions. Could the preservation of micro-loops help explain how daughter cells inherit a “memory” of previous gene expression states of the parent cell? Might diseases that involve dysregulated chromatin structure, such as cancer, stem from errors in these micro-loop regions during cell division? This research reinforces the idea that understanding genetic disorders or therapies involves more than identifying mutated genes. It also requires considering the spatial organization of the genome and how its 3D structure shapes expression.

    In summary, the article expands our perspective on genetics. It is not just about linear DNA sequence, mutation, and inheritance. It also includes how the genome is packaged, folded, and maintained within the nucleus, even as cells divide. Recognizing this adds a deeper layer to how we think about gene regulation in both health and disease.

Well-known Principle in Physics Applies to a Newly Discovered Biomolecular Mechanism in Mitosis

When cells divide via mitosis, their genetic information is passed onto both daughter cells--the process in which this occurs is highly complex. In this process, microtubules, which are small cylindrical protein tubes, are highly involved as they form the scaffold of the spindle apparatus. This scaffold aids in distributing the genome of the chromosomes to the two daughter cells when the cells divide. The microtubules also stabilize the spindle apparatus, where the microtubules overlap the center of each cell connecting the opposite spindle poles. When the cells divide, the microtubules have been observed to slide in relation to one another by what are called motor proteins; however, the sliding stops before the microtubules actually separate.

In general, little is known about the mechanical basis that takes place in mitosis--only small fragments have been understood. With regards to the mechanism described above, scientists did not understand what caused the microtubules to stop moving and sliding--until now. This mechanism, which is only a fragment in the entire mechanical mechanism in mitosis, can be explained by a well-known principle in physics. Gas particles in a closed container increase their pressure in response to a reduction in volume. Likewise, weakly binding proteins that accumulate between overlapping microtubules behave in the same manner; thus, counteracting the pressure between the overlapping microtubules as they slide apart. As a result, the gas-like pressure of the weakly binding proteins causes the movement of the microtubules to decelerate, and in turn stops the sliding, as well.

Scientists have demonstrated this mechanism by measuring the resulting forces using optical tweezers; thus, experimentally proving the newly found mechanism. Although the mechanism is minimal, it has been added to the entire collection of work of biological mechanisms of action. As studies continue to progress, more and more fragments of mechanisms will continue to be found, one day enabling the puzzle pieces to be finally put together.

Original Article: click here.
The actual study: click here.

Mitotic Cell Division Made More Clear

At any given moment thousands of cells are dividing by Mitosis in our bodies. During Mitosis the cell duplicates its genetic material and divides itself into two identical halves. If this process does not work efficiently it can lead to mutations which can cause diseases like cancer. A research on this complex mechanism was carried out by Manuel Mendoza and his team from Centre for Genomic Regulation (CRG) using yeast.

Mitotic Division in Cells 

When a cell prepares to divide, it duplicates its DNA into pairs of identical chromosomes. This chromosomes are tangled and twisted amongst themselves. For a cell division to occur, this twisted chromosomes have to be untangled, and that is where the enzyme Topoisomerase 2 (Topo 2) comes into play. Topo 2 cuts the DNA knots, untangles the knots between replicated chromosomes, and then ties back the ends afterwards so each pair of chromosome can migrate to the opposite ends of the cell.

It was thought that Topo 2 acted quickly and equally on all the chromosomes. But it was found that longer chromosomes need extra help to undo the knots. This extra help to Topo 2 is given by microtubules. Microtubules anchor to the chromosomes at a precise point and pull them apart towards opposite ends, so each cell gets its individual copy.

Mendoza and his research team noticed the speed at which the microtubules  pull the chromosome apart was constant. But, when a shorter chromosomes was under tension it would be untangled rapidly, on the other hand a longer chromosome took more time to come under tension (due to its long length), and therefore Topo 2 would finish untangling them for a longer time. The untangling only occurs when the microtubules begin to stretch the chromosomes (anaphase). Right up to that moment Topo 2 keeps doing its job.

It is surprising to know that not everything yet has been known about the Mitotic cell division as it is a  repetitive mechanism that has been occurring in our bodies from the beginning of time. I think it is essential that everything about it should be known, and this discovery about the role of Topoisomerase 2 is step towards knowing the proper functioning of cell division and hence higher survival of all the cells, and living beings.



Article: http://www.sciencedaily.com/releases/2014/09/140916101958.htm
Related Article: Mitosis -  http://www.nature.com/scitable/topicpage/mitosis-14046258