Nucleic acids,heredity and the functions of nucleotides and their definitions

1. Nucleotides, Nucleic Acids and Heredity
GOOD
MORNING!

2. The Molecules of Heredity
• Each cell of our bodies contains thousands of different
proteins.
• How do cells know which proteins to synthesize out of
the extremely large number of possible amino acid
sequences?
• From the end of the 19th century, biologists suspected
that the transmission of hereditary information took
place in the nucleus, more specifically in structures
called chromosomes.
• The hereditary information was thought to reside in
genes within the chromosomes.
• Chemical analysis of nuclei showed chromosomes are
made up largely of proteins called histones and nucleic
acids.

3. The Molecules of Heredity
• By the 1940s, it became clear that
deoxyribonucleic acids (DNA) carry the
hereditary information.
• Other work in the 1940s demonstrated
that each gene controls the manufacture
of one protein.
• Thus the expression of a gene in terms of
an enzyme protein led to the study of
protein synthesis and its control.

4. Nucleic Acids
There are two kinds of nucleic acids in
cells:
• Ribonucleic acids (RNA)
• Deoxyribonucleic acids (DNA)
Both RNA and DNA are polymers built
from monomers called nucleotides. A
nucleotide is composed of:
• A base, a monosaccharide, and a
phosphate.

5. Purine/Pyrimidine Bases
• The five principal bases of DNA and RNA.

6. Nucleosides
Nucleoside: A compound that consists of D-ribose or
2-deoxy-D-ribose bonded to a purine or pyrimidine base
by a -N-glycosidic bond.
H
H
H
H
O
HOCH2
HO OH
O
O
HN
N
anomeric
carbon
a b-N-glycosidic
bond
Uridine
b-D-riboside
uracil
1'
2'
3'
4'
5'
1

7. Nucleotides
Nucleotide: A nucleoside in which a molecule of phosphoric
acid is esterified with an -OH of the monosaccharide,
most commonly either at the 3’ or the 5’-OH.

8. Nucleotides
Deoxythymidine 3’-monophosphate (3’-dTMP),
O
H
H
H
H
O
H
HN
N
O
CH3
O
P
O O-
O-
HOCH2
5'
1'
3'

9. Nucleotides
Adenosine 5’-triphosphate (ATP) serves as a common
currency into which energy gained from food is
converted and stored.

10. DNA—Primary (1°) Structure
For nucleic acids, primary structure is
the sequence of nucleotides,
beginning with the nucleotide that has
the free 5’ terminus.
• The strand is read from the 5’end to
the 3’end.
• Thus, the sequence AGT means that
adenine (A) is the base at the 5’
terminus and thymine (T) is the base
at the 3’ terminus.

11. Structure of DNA and RNA
Schematic diagram of a
nucleic acid molecule. The
four bases of each
nucleic acid are arranged
in various specific
sequences. The base
sequence is read from the
5’ end to the 3’ end.

12. DNA—2° Structure
Secondary structure: The ordered
arrangement of nucleic acid strands.
• The double helix model of DNA 2°
structure was proposed by James
Watson and Francis Crick in 1953.
Double helix: A type of 2° structure of
DNA in which two polynucleotide
strands are coiled around each other
in a screw-like fashion.

13. THE DNA Double Helix
Three-
dimensional
structure of
the DNA
double helix.

14. Base Pairing
A and T pair by
forming two
hydrogen bonds.
G and C pair by
forming three
hydrogen bonds.

15. Superstructure of Chromosomes
DNA is coiled around proteins called histones.
• Histones are rich in the basic amino acids Lys and Arg,
whose side chains have a positive charge.
• The negatively-charged DNA molecules and positively-
charged histones attract one another and form units
called nucleosomes.
Nucleosome: A core of eight histone molecules around
which the DNA helix is wrapped.
• Nucleosomes are further condensed into chromatin.
• Chromatin fibers are organized into loops, and the
loops into the bands that provide the superstructure of
chromosomes.

16. Superstructure of Chromosomes

17. DNA and RNA
The three differences in structure
between DNA and RNA are:
• DNA bases are A, G, C, and T; the
RNA bases are A, G, C, and U.
• the sugar in DNA is 2-deoxy-D-
ribose; in RNA it is D-ribose.
• DNA is always double stranded;
there are several kinds of RNA, all of
which are single-stranded.

18. Information Transfer

19. RNA
The roles of Different kinds of RNA
RNA type Size Function
Small nuclear
RNA (snRNA
Small Processes intitial mRNA to its
mature form in eukaryotes.
Small intefering
RNA(siRNA)
Transfer RNA
(tRNA)
Small Transports amino acids
to site of protein synthesis
Ribosomal RNA
(rRNA)
Several kinds;
variable in size
Combines with proteins to
form ribosomes,
the site of protein synthesis.
Messenger RNA
(mRNA)
Variable Directs amino sequence of
proteins.
Small Affects gene expression ; used
by scientists to knock out gene
being studied.
Micro RNA
(miRNA)
Small Affects gene expressions;
important in growth and
development

20. Structure of tRNA
Structure of tRNA.

21. Structure of rRNA
The structure of a typical
prokaryotic ribosome.

22. Ribosome

23. Roles of Different kinds of RNA

24. Genes, Exons, and Introns
Gene: A segment of DNA that carries a base
sequence that directs the synthesis of a
particular protein, tRNA, or mRNA.
• There are many genes in one DNA molecule.
• In bacteria, the gene is continuous.
• In higher organisms, the gene is
discontinuous.
Exon: A section of DNA that, when transcribed,
codes for a protein or RNA.
Intron: A section of DNA that does not code for
anything functional.

25. Genes, Exons, and Introns
• The properties of mRNA molecules in prokaryotes cells
during transcription and translation.

26. Replication of DNA
The DNA in the chromosomes carries out
two functions:
• (1) It reproduces itself. This process is
called replication.
• (2) It supplies the information necessary
to make all the RNA and proteins in the
body, including enzymes.
Replication begins at a point in the DNA
called the origin of replication or a
replication fork.

27. Replication of DNA
General features of the replication of DNA. The two
strands of the DNA double helix are shown separating at
the replication fork.

28. Replication of DNA
The replication of DNA occurs in number of distinct steps.
1. Opening up of the superstructure of the chromosomes.
One key step is this process is acetylation-
deacetylation of lysine residues on histones. This
reaction eliminates some of the positive charges on
histones and weakens the strength of the DNA-histone
interaction.

29. Replication of DNA
2. Relaxation of Higher-Order Structures of DNA.
Tropoisomerases (also called gyrases) temporarily
introduce either single-or double strand breaks in
DNA.
Once the supercoiling is relaxed, the broken strands
are joined together and the tropoisomerase diffuses
from the location of the replication fork.
3. Replication of DNA molecules starts with the
unwinding of the double helix which can occur at
either end or in the middle. Special unwinding
proteins called helicases, attach themselves to one
DNA strand and cause the separation of the double
helix.

30. Replication of DNA
4. Primers/Primases
Primers are short—4 to 15 nucleotides long—RNA
oligonucloetides synthesized from ribonucleoside
triphosphates. They are needed to initiate the primase-
catalyzed synthesis of both daughter strands.
5. DNA Polymerase
Once the two strands are separated at the replication
fork, the DNA nucleotides must be lined up. In the
absence of DNA polymerases, this alignment is
extremely slow. The enzyme enables complementary
base pairing with high specificity. While bases are
being hydrogen bonded to their partners, polymerases
join the nucleotide backbones.

31. Replication of DNA
Along the lagging strand 3’—>5”, the enzymes can
synthesize only short fragments, because the only
way they can work is from 5’ to 3’. These resulting
short fragments consist of about 200 nucleotides
each, named Okazaki fragments after their
discoverer.
6. Ligation
The Okazaki fragments and any nicks remaining are
eventually joined by DNA ligase.

32. How Do We Amplify DNA?
• To study DNA for basic and applied scientific purposes,
we must have enough of it to work with.
• Millions of copies of selected DNA fragments can be made
within a few hours with high precision by a technique
called polymerase chain reaction (PCR).
• To use PCR, the sequence of a gene to be copied or at
least a sequenced segment bordering the desired DNA
must be known.
• In such a case, two primers that are complementary to
the ends of the gene or to the bordering DNA can be
synthesized. The primers are polynucleotides
consisting of 12 to 16 nucleotides. When added to the
target DNA segment, they hybridize with the end of
each strand of the gene.

33. How Do We Amplify DNA?
• Polymerase chain reaction
(PCR). Oligonucleotides
complementary to a given
DNA sequence prime the
synthesis of only that
sequence.

34. How Do We Amplify DNA
A polymerase extends the primers in each direction as
individual nucleotides are assembled and connected on
the template DNA. In this way two copies are created.
The two-step process is repeated (cycle 2) when the
primers are hybridized with new strands and the primers
extended again. At this point, four new copies have been
created. The process is continued, and in 25 cycles, 225 or
some 33 million copies can be made.
This process is practical because of the discovery of
heat-resistant polymerases isolated from bacteria that live
in hot thermal vents on the sea floor. A temperature of
95°C is required to unwind the double helix to hybridize
the primer to the target DNA.

35. How Is DNA repaired?
• The viability of cells depends on DNA repair enzymes that
can detect, recognize, and remove mutations from DNA.
• Externally, UV radiation or highly reactive oxidizing
agents, such as superoxide, may damage a base.
• Errors in copying or internal chemical reactions, such as
deamination of a base,can create damage internally
Deamination of cytosine turns it into uracil, which creates
a mismatch. The former C-G base pair becomes a U-G
mispair that must be removed.
• One of the most common base repair prepare means is
called BER, base excision repair .

36. How Is DNA repaired?
• The BER pathway contains two parts:
• 1. A specific DNA glycolase (1) recognizes the damaged
base and catalyzes the hydrolysis of the -glycosidic
bond between the uracil base base and the deoxyribose,
then releases the damaged base completing the excision.
The sugar-phosphate backbone is still intact. At the AP
site (apurinic or apyrimidinic site) created in this way, (2)
the backbone is cleaved by a second enzyme,
endonuclease. A third enzyme, exonuclease (3), liberates
the sugar-phosphate unit of the damaged site.
• 2. In the synthesis step, the enzyme DNA polymerase (4)
inserts the correct nucleotide, cytidine, and the enzyme
DNA ligase seals (5) the backbone to complete the repair.

37. Nucleotides, Nucleic Acids and Heredity
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