Humane levenscyclus 1. Deeltoets 1
OOK CHAPTER 2 PANEL 2-6, 2-7 EN AANTEKENINGEN
HC 2: Celbiologie en DNA Chapter 5
STRUCTURE OF DNA (deoxyribonucleic acid)
Life depends on the stable storage, maintenance, and inheritance of genetic information.
DNA is made of four nucleotide building blocks. (A)
Each nucleotide is composed of a sugar phosphate
covalently linked to a base—guanine (G) in this
figure. (B) The nucleotides are covalently linked
together into polynucleotide chains, with a sugar–
phosphate backbone from which the bases—
adenine, cytosine, guanine, and thymine (A, C, G,
and T)—extend. (C) A DNA molecule is composed of
two polynucleotide chains (DNA strands) held
together by hydrogen bonds between the paired
bases. The arrows on the DNA strands indicate the
polarities of the two strands, which run antiparallel
to each other (with opposite chemical
polarities/complementary) in the DNA molecule. (D)
Although the DNA is shown straightened out in (C),
in reality, it is wound into a double helix (D).
The nucleotide subunits within a DNA strand are held together by
phosphodiester bonds. These bonds connect one sugar to the next.
The chemical differences in the ester linkages—between the 5ʹ
carbon of one sugar and the 3ʹ carbon of the other—give rise to the
polarity of the resulting DNA strand (3’ OH (downstream) and 5’
(upstream) Phosphate, coding 5’ 3’).
In each case, a bulkier two-ring base (a purine; A/G) is paired with a
single-ring base (a pyrimidine; C/U/T), a base pair.
THE STRUCTURE OF EUKARYOTIC CHROMOSOMES
The genetic material of a eukaryotic cell—its genome—is contained
in a set of chromosomes, each formed from a single, enormously
long DNA molecule that contains many genes.
The maternal and paternal chromosomes are called homologous
chromosomes (homologs). The nonhomologous chromosomes pairs
are the sex chromosomes (XX/XY) (p=short, q=long)
Gametes=sperm and eggs
Karyotype=an ordered display of the full set of 46 human chromosomes (detecting abnormalities)
When a gene is expressed, part of its nucleotide sequence is transcribed into RNA molecules, most of
which are translated to produce a protein.
In many eukaryotes, genes include an excess of interspersed, noncoding DNA. This excess of DNA is
often called junk DNA, but it does have a biological function.
Three DNA sequence elements are needed to produce a eukaryotic chromosome that can be
duplicated and then segregated at mitosis. Each chromosome has multiple origins of replication,
one centromere, and two telomeres. The DNA replicates in interphase, beginning at the origins of
replication and proceeding bidirectionally from each origin along the chromosome. In M phase, the
centromere attaches the compact, duplicated chromosomes to the mitotic spindle so that one copy
will be distributed to each daughter cell when the cell divides. Prior to cell division, the centromere
also helps to hold the duplicated chromosomes together until they are ready to be pulled apart.
Telomeres contain DNA sequences that allow for the complete replication of chromosome ends.
Interphase chromosome=not visible, Mitotic chromosomes=visible
Interphase chromosomes occupy their own distinct territories within the nucleus. Note that pairs
of homologous chromosomes, such as the two copies of chromosome 3, are not generally located in
the same position.
The nucleolus is the most prominent structure in
the interphase nucleus. The nucleus is surrounded
by the nuclear envelope. Inside the nucleus, the
chromatin appears as a diffuse speckled mass;
regions that are especially dense are called
heterochromatin (dark staining). Heterochromatin
contains few genes and is located mainly around the
periphery of the nucleus, immediately under the
nuclear envelope. The large, dark region within the
nucleus is the nucleolus, which contains the genes
for ribosomal RNAs.
chromosomes, the DNA is tightly folded by binding to a set of histone
and nonhistone chromosomal proteins. This complex of DNA and protein
is called chromatin.
Histones pack the DNA into a repeating array of DNA–protein particles
called nucleosomes, which further fold up into even more compact
Nucleosomes contain DNA wrapped around a protein core of eight
histone molecules. In a test tube, the nucleosome core particle can be
released from chromatin by digestion of the linker DNA with a nuclease,
which cleaves the exposed linker DNA (breaks phosphodiester bond) but
not the DNA wound tightly around the nucleosome core. When the DNA
around each isolated nucleosome core particle is released, its length is
found to be 147 nucleotide pairs; this DNA wraps around the histone
octamer that forms the nucleosome core nearly twice.
The positive charges help the histones bind tightly to the negatively charged sugar–phosphate
backbone of DNA. These numerous electrostatic interactions explain in part why DNA of virtually any
sequence can bind to a histone octamer.
The chromatin in human chromosomes is folded into looped domains. These loops are established
by special nonhistone chromosomal proteins that bind to specific DNA sequences, creating a clamp
at the base of each loop.
DNA packing occurs on several levels in chromosomes.
This schematic drawing shows some of the levels
thought to give rise to the highly condensed mitotic
chromosome. Both histone H1 and a set of specialized
nonhistone chromosomal proteins are known to help
drive these condensations, including the chromosome
loop-forming clamp proteins and the abundant non-
histone protein condensin.
REGULATION OF CHROMOSOME STRUCTURE
A cell can regulate its chromatin structure—temporarily
decondensing or condensing particular regions of its
chromosomes—using chromatin-remodeling complexes
and enzymes that covalently modify histone tails in
various ways (dynamic).
Chromatin-remodeling complexes locally reposition the DNA
wrapped around nucleosomes. The complexes use energy
derived from ATP hydrolysis to loosen the nucleosomal DNA
and push it along the histone octamer. In this way, the
enzyme can expose or hide a sequence of DNA, controlling its
availability to other DNA-binding proteins. The blue stripes
have been added to show how the DNA shifts its position.
Many cycles of ATP hydrolysis are required to produce such a shift.
The pattern of modification of histone tails can determine how a stretch of chromatin is handled
by the cell. Each histone can be modified by the covalent attachment of a number of different
chemical groups, mainly to the tails. . The tail of histone H3, for example, can receive acetyl groups
(Ac), methyl groups (M), or phosphate groups (P). Most modifications occur on the N-terminal tail. )
Different combinations of histone tail modifications can confer a specific meaning on the stretch of
chromatin on which they occur (modifications (direct) and protein binding to modifications (indirect).
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