How do nucleosomes keep our DNA from reaching the sun?

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Todd Smith
A key concept in science is molecular scale. DNA is a fascinating molecule in this regard. While we cannot "see" DNA molecules without the aid of advanced technology, a full length DNA molecule can be very long. In human cells, other than sperm and eggs, six billion base pairs of DNA are packaged into 22 pairs of chromosomes, plus two sex chromosomes. Each base pair is 34 angstroms in length (.34 nanometers, or ~0.3 billionths of a meter), so six billion base pairs (all chromosomes laid out head to toe) form a chain that's two-meters long. If we could hang this DNA chain from a hook, it would be slightly taller than an average human [2]. But that's just the DNA from one cell. Each of us have around 50 trillion cells (50,000 billion).  If we took the DNA from all of those cells and laid it out in a linear fashion, it could wrap around the earth 2.5 million times, or reach to the sun and back 300 times [3]! Yet cells manage to pack all that DNA into a structure so small we can't even see it without a microscope. How does this happen?
IMG_0191 Nucleosome from [4] in Molecule World using space fill and element coloring

Biology solves the packing problem with nucleosomes. In the early 1900's scientists understood that chromosomes contained genes [4]. When stained, these colorful bodies, could be observed under the microscope and scientists determined that chromosomes contained both protein and DNA. As you might know, genes are DNA.  In a chromosome, DNA is packed into a smaller structure by winding it around a set of histone proteins, just like you might pack up a cord by winding it around your hand.  This compact structure is the nucleosome [3]. The first publication of a nucleosome structure was in 1997 [5]. Since then, many hundreds of nucleosome structures have been added to public databases like the PDB (the Protein Data Bank) and MMDB (the Molecular Modeling Database). Nearly 100 of these structures from a variety of organisms (humans, cows, chickens, frogs, and yeast) show how DNA wraps around a core of histone proteins. Some of these structures were solved and published to understand the interactions between the proteins and DNA and  the implications of the higher-order structure.  Other nucleosome structures were solved in order to study the effects of mutations in DNA sequences or histone proteins.  The changes in these structures are interesting to researchers because nucleosomes play an important role in DNA accessibility.  The accessibility or inaccessiblity of DNA to enzymes like RNA polymerase, for example, is important for normal cellular function and, when disrupted, can contribute to diseases like cancer.  Hence, nucleosomes can be good targets for drugs that treat cancer or act by inhibiting transcription. In  Molecule World™, you can explore these structures and learn about the chemical properties of the molecules that make up these structures and investigate their interactions.
IMG_0192 Structure showing the DNA "supergroove" with a polyamide dimer bound (white) [6]. Space fill with charge highlighted in Molecule World.

IMG_0193 Structure with molecule highlighting in Molecule World showing the individual strands of DNA and histone proteins in different colors.

References 1. Next Generation Science Standards: From molecules to Organisms ( 2. Average human height: 3. DNA Packaging: 4. Sutton, W. (1903). The Chromosomes in Heredity Biological Bulletin, 4 (5) DOI: 10.2307/1535741 5. Luger K, Mäder AW, Richmond RK, Sargent DF, & Richmond TJ (1997). Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature, 389 (6648), 251-60 PMID: 9305837 PDB ID: 1AOI  6. Edayathumangalam RS, Weyermann P, Gottesfeld JM, Dervan PB, & Luger K (2004). Molecular recognition of the nucleosomal "supergroove". Proceedings of the National Academy of Sciences of the United States of America, 101 (18), 6864-9 PMID: 15100411 PDB ID: 1S32 Molecule World™ was developed with funding from the National Science Foundation (SBIR IIP 1315426).  Any opinions, findings, conclusions, or recommendations expressed on this website are those of the authors and do not necessarily represent the official views, opinions, or policy of the National Science Foundation.

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