In this document, you can find a summary of the course Molecular Genetics which is given in the second year of Biology / Life Science and Technology (old curriculum) at the University of Groningen.
For this summary, the book Molecular Biology of the Cell is used.
Summary Molecular Biology of the Cell 2 (book) (WBFA007-04)
Summary Regenerative Medicine
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Rijksuniversiteit Groningen (RuG)
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Molecular Genetics (WBBY00805)
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Chapter 4: DNA, Chromosomes and Genomes
THE STRUCTURE AND FUNCTION OF DNA
Genes = the information-containing elements that determine the characteristics of a species as a whole
and of the individuals within in.
o A deoxyribonucleic acid (DNA) molecule consist of two long polynucleotide chains (DNA strands)
composed of four types of nucleotide subunits (adenine (A), cytosine (C), guanine (G) and
thymine (T)).
o The nucleotides are composed of a sugar called deoxyribose, a single phosphate group and a
base.
o The nucleotides are covalently linked together in a chain through the sugars and phosphates,
which thus from a ‘’backbone’’ of alternating sugar-phosphate-sugar-phosphate.
o Complementary base-pairing (A-T (2 H-bonds); G-C (3 H-bonds)) enables the base pairs to be
packed in the energetically most favorable arrangement in the interior of the double helix.
o A consequence of DNA’s structure and base-pairing requirements is that each strand of a DNA
molecule contains a sequence of nucleotides that is exactly complementary to the nucleotide
sequence of its partner strand.
Purine = two-ring base (A and G).
Pyrimidine = single-ring base (T and C).
o Each strand can acts as a template, or mold, for the synthesis of a new complementary strand.
Genome = the complete store of information in an organism’s DNA and it specifies all the RNA molecules
and proteins that the organism will ever synthesize.
CHROMOSOMAL DNA AND ITS PACKAGING IN THE CHROMATIN FIBER
o Each chromosome in a eukaryotic cell consists of a single, enormously long linear DNA molecule
along with the proteins that fold and pack the fine DNA thread into a more compact structure.
Chromatin = the complex of DNA and tightly bound protein.
Homologous chromosomes (homologs) = the maternal and paternal chromosomes of a pair.
- Each human cell contains a total of 46 chromosomes – 22 pairs common to both males and
females, plus two so-called sex chromosomes (XX/XY).
o There is no simple relationship between chromosome number, complexity of the organism, and
total genome size. The genomes and chromosomes of modern-day species, have each been
shaped by unique history of seemingly random genetic events.
Exons = the coding sequences.
Introns = the intervening (non-coding) sequences.
Cell cycle = a temporal separation between the duplication of chromosomes and their segregation into
two daughter cells.
DNA replication origin = the location at which duplication of the DNA begins.
- Eukaryotic chromosomes contain many origins of replication to ensure that the entire
chromosome can be replicated rapidly.
o The presence of a second specialized DNA sequence, called a centrosome, allows one copy of
each duplicated and condensed chromosome to be pulled into each daughter cell when a cell
divides.
,Telomers = contain repeated nucleotide sequences that enable the ends of chromosomes to be
efficiently replicated and protect the end of the chromosome.
o The proteins that bind to the DNA to form eukaryotic chromosomes are
traditionally divided into two classes: the histones and the non-histone
chromosomal proteins.
Chromatin = the complex of both classes of protein with the nuclear DNA of
eukaryotic cells.
o Histones are responsible for the first and most basic level of chromosome
packing, the nucleosome.
o Most of the chromatin appears to be in the form of a fiber with a
diameter of about 30 nm.
Linker DNA = the exposed DNA between the nucleosome core particles.
o Each individual nucleosome core particle consists of a complex of 8
histone proteins – two molecules each of histone H2A, H2B, H3 and H4.
o Numerous hydrophobic interactions, hydrogen bonds and salt linkages
hold DNA and protein together in the nucleosome.
o Each of the core histones has an N-terminal amino acid ‘’tail’’, which
extends out from the DNA-histone core. This histone tails are subject to several different types
of covalent modifications that in turn control critical aspects of chromatin structure and
function.
o The exact position of nucleosomes along the stretch of DNA depends mainly on the presence
and nature of other proteins bound to the DNA.
o Due to the presence of ATP-dependent chromatin remodeling complexes, the arrangement of
nucleosomes on DNA can be highly dynamic, changing rapidly according to the needs of the cell.
o The structure of a tetranucleosome (a complex of four nucleosomes) is a zigzag model for the
stacking of nucleosomes in a 30 nm fiber.
o One important factor of nucleosome-to-nucleosome linkages that involves histone tails is the H4
tail.
o Another important factor is histone H1 (linker histone). A H1 molecule binds to each
nucleosome, containing both DNA and protein, and changing the path of the DNA as it exits from
the nucleosome; this change in the exit path of DNA is thought to help compact nucleosomal
DNA.
CHROMATIN STRUCTURE AND FUNCTION
Heterochromatin = highly condensed, especially compact form of chromatin. A descriptor for compact
chromatin domains that share the common feature of being unusually resistant to gene expression.
Euchromatin = less condensed from of chromatin.
o The amino acid side chains of the four histones in the nucleosome core are subjected to a
remarkable variety of covalent modifications. These modifications are reversible, with one
enzyme serving to create a particular type of modification, and another to remove it.
o For example: acetyl groups are added to specific lysines by a set of different histone acetyl
transferases (HATs) and removed by a set of histone deacetylase complexes (HDACs).
o Each enzyme is recruited to specific sites on the chromatin at defined times in each cell’s life
history.
o The tight packaging of the DNA into heterochromatin usually silences (inactivating) the genes
within it.
, THE GLOBAL STRUCTURE OF CHROMOSOMES
o Chromosomes are folded into large loops of chromatin. The majority of the DNA is not in loops
but remains highly condensed on the chromosome axis, where genes are generally not
expressed.
o Highly folded loops of chromatin expand to occupy an increased volume when a gene within
them is expressed.
o Each of the 46 interphase chromosomes in a human cell tends to occupy its own discrete
territory within the nucleus: chromosomes are not extensively entangled with one another.
o The nucleus is very heterogeneous, with functionally different regions to which portions of
chromosomes can move as they are subjected to different biochemical processes – such as when
their gene expression changes.
o The nuclear matrix, or scaffold, contains of proteins and RNA molecules that form a insoluble
materials that are likely to be derived from the fibrous subcompartments of the nucleolus, while
others may be proteins that help to form the base of chromosomal loops or to attach
chromosomes to other structures in the nucleus.
o The DNA molecules produced by DNA replication during interphase of the cell-division cycle are
separately folded to produce two sister chromosomes, or sister chromatids, held together at
their centromeres.
o The compaction of chromosomes during mitosis is a highly organized and dynamic process that
serves at least two important purposes:
1. When condensation is complete, sister chromatids have been disentangled from each other and
lie side by side, by which they can easily separate when the
mitotic apparatus begin pulling them apart.
2. The compaction of chromosomes protects the relatively fragile
DNA molecules from being broken as they are pulled to
separate daughter cells.
o Mitotic chromosome condensation can be thought of as the
final level in the hierarchy of chromosome packaging.
Chapter 5: DNA replication, Repair and Recombination
THE MAINTENANCE OF DNA SEQUENCES
o Occasional genetic changes enhance the long-term survival of a
species through evolution, the survival of the individual
demands a high degree of genetic stability.
Mutation = a permanent change in the DNA.
o Many mutations are silent, those that change a codon but not the amino acid it specifies, or
those that change an amino acid without affecting the activity of the protein coded for by the
gene.
DNA REPLICATION MECHANISMS
o Deoxyribonucleoside triphosphates (dNTPs), DNA polymerase and a single-strand DNA template
is needed for DNA replication.
o Each of the two daughters of a dividing cell inherits a new DNA double helix containing the
original and one new strand, the DNA double helix is said to be replicated ‘’semiconservatively’’.
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