MCAT Biochemistry Review

Chapter 6: DNA and Biotechnology

6.2 Eukaryotic Chromosome Organization

There are over 6 billion bases of DNA in each human cell. It is important for the cell to organize these bases effectively. These bases must be replicated during the cell cycle and also utilized in gene expression for normal cellular functions. In humans, DNA is divided up among the 46chromosomes found in the nucleus of the cell. The supercoiling of the DNA double helix does provide some compaction, but much more is necessary.

HISTONES

The DNA that makes up a chromosome is wound around a group of small basic proteins called histones, forming chromatin. There are five histone proteins found in eukaryotic cells. Two copies each of the histone proteins H2AH2BH3, and H4 form a histone core and about 200 base pairs of DNA are wrapped around this protein complex, forming a nucleosome, as shown in Figure 6.10. Under an electron microscope, the nucleosomes look like beads on a string. The last histone, H1, seals off the DNA as it enters and leaves the nucleosome, adding stability to the structure. Together, the nucleosomes create a much more organized and compacted DNA.

Figure 6.10. Nucleosome Structure Nucleosomes are composed of DNA wrapped around histone proteins.

Histones are one example of nucleoproteins (proteins that associate with DNA). Most other nucleoproteins are acid-soluble and tend to stimulate processes such as transcription.

HETEROCHROMATIN AND EUCHROMATIN

The chromosomes have a diffuse configuration during interphase of the cell cycle. The cell will undergo DNA replication during the S phase of interphase and having the DNA uncondensed and accessible makes the process more efficient. A small percentage of the chromatin remains compacted during interphase and is referred to as heterochromatin. Heterochromatin appears dark under light microscopy and is transcriptionally silent. Heterochromatin often consists of DNA with highly repetitive sequences. In contrast, the dispersed chromatin is called euchromatin, which appears light under light microscopy. Euchromatin contains genetically active DNA. Both heterochromatin and euchromatin can be seen in the nucleus in Figure 6.11.

Figure 6.11. Euchromatin and Heterochromatin in an Interphase Nucleus

KEY CONCEPT

Heterochromatin is dark, dense, and silent. Euchromatin is light, uncondensed, and expressed.

TELOMERES AND CENTROMERES

As described below, DNA replication cannot extend all the way to the end of a chromosome. This will result in losing sequences and information with each round of replication. The solution for our cells is a simple repeating unit (TTAGGG) at the end of the DNA, forming a telomere. Some of the sequence is lost in each round of replication and can be replaced by the enzyme telomerase. Telomerase is more highly expressed in rapidly dividing cells. Animal studies indicate that there are a set number of replications possible, and that the progressive shortening of telomeres contributes to aging. Telomeres also serve a second function: their high GC-content creates exceptionally strong strand attractions at the end of chromosomes to prevent unraveling; think of telomeres as “knotting off” the end of the chromosome.

Centromeres, as their name suggests, are a region of DNA found in the center of chromosomes. They are often referred to as sites of constriction because they form noticeable indentations. This part of the chromosome is composed of heterochromatin, which is in turn composed of tandem repeat sequences that also contain high GC-content. During cell division, the two sister chromatids can therefore remain connected at the centromere until microtubules separate the chromatids during anaphase.

MCAT Concept Check 6.2:

Before you move on, assess your understanding of the material with these questions.

1.    What are the five histone proteins in eukaryotic cells? Which one is not part of the histone core around which DNA wraps to form chromatin?

2.    Compare and contrast heterochromatin and euchromatin based on the following characteristics:

Characteristic

Heterochromatin

Euchromatin

Density of chromatin packing

   

Appearance under light microscopy

   

Transcriptional activity

   

3.    What property of telomeres and centromeres allow them to stay tightly raveled, even when the rest of DNA is uncondensed?