DNA Packaging
DNA Packaging
DNA Packaging
Part III
DNA Packaging
Reger Kornberg in 1974 reported that chromosome is made up of DNA and protein. The
organization of DNA is much more complex in eukaryotes.
Each chromosome contains a single DNA molecule, extending from one end of
the chromosome to the other end. DNA molecule is coiled and folded many times and
associated with various proteins, forming a “chromatin” which contains roughly equal
amounts of DNA and proteins. The chromosomal proteins are divided into Histone
proteins and Non-Histone proteins.
Histones are the proteins that facilitate the DNA packaging into chromatin fibres.
Histone proteins are positively charged and have many arginine and lysine amino acids
that bind to the negatively charged DNA. Histones are of two types:
Core Histones
Linker Histones
H2A, H2B, H3 and H4 are the core histones. Two H3, H4 dimers and two H2A, H2B
dimers form an octamer.
Linker histones lock the DNA in place onto the nucleosome and can be removed for
transcription.
Paper –V, Cytology B.Sc. Part III
Histones can be modified to change the amount of packaging a DNA does. The addition
of methyl group increases the hydrophobicity of histones. This results in tight DNA
packaging. Acetylation and phosphorylation make the DNA more negatively charged
and loosens the DNA packaging.
Packaging of DNA:
At the first level of packaging the DNA double helix is packaged into so-called
nucleosomes: sets of about 200 base pairs of the DNA are wound round a nucleus of
eight proteins, the histones. Due to their amino acid composition the histone proteins
are positively charged, but they can be modified by enzymes, so that their total charges
changes. Thus, a certain class of enzymes – histone acetyl transferases – cause acetyl
moieties to be attached, thereby neutralizing the intrinsic charge of the histones.
Another class of enzymes – histone deacetylases – can remove these acetyl moieties
again and thereby restore the positive intrinsic charge of the histones. Since the
components of the DNA – the nucleotides – are negatively charged, the charge state of
the histones assumed to have considerable influence on the packaging density of the
DNA in the chromatin.
Paper –V, Cytology B.Sc. Part III
Most of the time, DNA is loosely packaged. A DNA molecule in this form is about seven
times shorter than the double helix without the histones, and the beads are about 10 nm
in diameter, in contrast with the 2-nm diameter of a DNA double helix. The next level of
compaction occurs as the nucleosomes and the linker DNA between them are coiled
into a 30-nm chromatin fiber. This coiling further shortens the chromosome so that it is
now about 50 times shorter than the extended form. In the third level of packing, a
variety of fibrous proteins is used to pack the chromatin. These fibrous proteins also
ensure that each chromosome in a non-dividing cell occupies a particular area of the
nucleus that does not overlap with that of any other chromosome.
DNA replicates in the S phase of interphase. After replication, the chromosomes are
composed of two linked sister chromatids. When fully compact, the pairs of identically
packed chromosomes are bound to each other by cohesion proteins. The connection
between the sister chromatids is closest in a region called the centromere. The
conjoined sister chromatids, with a diameter of about 1 µm, are visible under a light
microscope. The centromeric region is highly condensed and thus will appear as a
constricted area.
Regions that are necessary for making proteins and are important for the cell are
loosely packed and called euchromatin. By having a loose packing of DNA in
Paper –V, Cytology B.Sc. Part III
euchromatin, proteins involved in transcription can easily get in and make RNA. On
the other hand, some regions of DNA which are called heterochromatin and are tightly
packed through DNA as well as through good ol' histone methylation.