Cancer and Genetics:

1
Cancer and Genetics Whats the Connection?
Supported by a grant from the National Cancer
Institute 1R25CA93426 Administered
through the Oncology Nursing Society
2
Part II DNA Replication
3
Central Dogma of Molecular Genetics
trans- scription
trans- lation
DNA
RNA
Protein
4
Mitosis The process of cell division whereby
one cell duplicates to become two cells, exactly
the same as the original cell for genetic
constitution. Requires leaving the
reproductive resting state of G0 and entering the
cell cycle.
5
Ignatavicius, D., Workman, M.L. (2002).
Medical-surgical nursing Critical thinking for
clinical care. Philadelphia W.B. Saunders
6
(No Transcript)
7
(No Transcript)
8
Enzyme Participation
A variety of enzymes and other proteins
are required for DNA replication. Some of the
activities of these proteins include Nicking and
Closing the DNA Relaxing the DNA Unwinding
the DNA Keeping the strands separated
Initiation of DNA synthesis Elongating the DNA
chain Linking new sections of DNA together
Editing repairing DNA errors
9
Enzyme Participation
DNA Polymerases several subtypes
actions Chain elongation Proofreading DNA
repair (exonuclease activity) DNA ligase
connects new DNA segments together DNA helicases
unwinds DNA separating the double strands
10
Enzyme Participation
DNA topoisomerases create a transient nick
to disrupt supercoils RNA polymerases primase
create a short and temporary RNA primer that
initiates new DNA synthesis Single-stranded
DNA-binding proteins (SSB proteins) Help keep
strands separated long enough for transcription
to take place
11
Part III Protein Synthesis
12
Central Dogma of Molecular Genetics
trans- scription
trans- lation
DNA
RNA
Protein
13
Gene Function The purpose of a gene is to code
for the synthesis of a specific protein used by a
cell, tissue, or organ within the person. For
example, the hormone insulin is a protein. When a
persons blood glucose level starts to rise, the
beta cells of the pancreas first release a very
small amount of insulin that has already been
made. But the bigger response will be the rapid
synthesis of new insulin to meet the immediate
needs of the person for blood glucose
homeostasis.
14

• Genes serve as templates for the transcription of
  RNA. Messenger RNA serves as a "recipe" for the
  correct manufacture of a specific protein.

15
Transcription
When a protein is going to be made, only the
segment of original DNA that contains the gene
for that protein is opened and copied or
transcribed into RNA.
16
A T G C G C C G T A C G A T A T C G C G
T A G C
Strand 2
Strand 1
G G C U C A A C C U
Transcription
mRNA
17
Transcription for Protein synthesis
The result of this transcription is the formation
of a strand of RNA that contains the codes for
the amino acid sequence of a specific
protein. Once the transcription is completed, the
DNA strands close back into the helical state.
Figure from the National Human Genome Research
Institute (NIH)
18
Figure from the National Cancer Institute_at_
http//press2.nci.nih.gov/sciencebehind
19
RNA RNA or ribonucleic acid, is a single
strand of nitrogenous bases (adenine,
guanine, cytosine, and uracil) constructed
during transcription from a segment of
DNA containing a gene for a specific protein. The
RNA is complementary to the "template" DNA. A
major difference in RNA is the use of the base
"uracil" in place of thymine.
20
H
H
O
O
CH3
N
N
O
H
H
O
N
N
Uracil
Thymine
21
RNA
RNA Codons
C C U ACU A G C AGGCUCAGU
C
Codon 1
C
U
A
C
Codon 2
U
A
G
Codon 3
C
A
Codon 4
G
G
C
Codon 5
U
C
A
Codon 6
G
U
22
Codons for Individual Amino Acids
Ala GCU, GCC, GCA, GCG Lys AAA, AAG
Phe UUU, UUC Ser UCU, UCG Val GUU, GUC, GUA,
GUG Start AUG Stop UAA, UAG, UGA
23
sense ---C-A-G-T-A-C-C-A-A-G-T-G-A-T antisense
-G-T-C-A-T-G-G-T-T-C-A-C-T-A
transcription with RNA polymerase mRNA
G-U-C-A-U-G-G-U-U-C-A-C-U-A
24
DNA T-A-G-A-C-A-G-T-A-C-C-A-A-G-T-G-A-T RNA A-U
-C-U-G-U-C-A-U-G-G-U-U-C-A-C-U-A
25
T- A -G-A-C-A-G-T-A-C-C-A- A-G-T-G-A-T mRNA
C-U-G-C-A-U-U-C-A
26
Exon
The region of the DNA within a gene area that is
expressed or actually codes for the protein.
Genes in humans and, many higher life forms, are
in DNA pieces or a discontinuous, rather than
a continuous series of bases corresponding to
the specific amino acid sequence. The exons
within a gene are separated from each other by
additional pieces of DNA that are not part of
the codes for that gene.
27
Intron
The regions of the DNA within a gene area that do
not codes for the protein currently being made.
These were originally called intervening
sequences and are now termed introns. Introns
in a gene reading area for one gene are not part
of that gene but are probably exons for a
different gene in the same area. Introns must be
spliced and removed from the final or mature
mRNA before translation occurs. Introns should
not be confused with desert DNA, the multiple
repeat sequences of DNA that separate gene coding
regions from one another.
28
Figure from the Roche Genetics Education Program
Collection
29
Figure from the Roche Genetics Education Program
Collection
30
Translation
Moving the transcribed mRNA into the endoplasmic
reticulum and generating a protein whose amino
acid sequence (encoded in the gene) was
transcribed into the mRNA. This process
requires energy, some special additional types
of RNA, and adequate amounts of individual amino
acids.
31
Primary Protein Structure
Ala
Phe
Val
Lys
Ser
Leu
Gly
32
The multi-step Process of Protein Synthesis
Figure from the National Human Genome Research
Institute (NIH)
33
Amino acid binding site
Phe
tRNA
3
5
Anticodon (pairs with a complementary codon on
mRNA)
A A G
CUG UUC CCC AUG ACC AGA UAU
mRNA
34
Ribosomes
GAG
AUG GCC UUU GUC UCA AAA CUC GGU AAU GAC
AGU
mRNA
35
Ala
Growing protein chain
Phe
Val
Ser
Lys
Leu
Ribosomes
tRNA
Start codon
GAG
AUG GCC UUU GUC UCA AAA CUC GGU AAU GAC
AGU
mRNA
36
AUG CAC GUC AGA CGG ACG CGA CCC UUU CUA
GUC GUA GCC UCA CUC
37
Point Mutation
Substitution of one base for another - may or may
not alter amino acid position or protein synthesis
38
THE BIG DOG ATE THE CAT
THE BIG DOG ATE THE CAP
39
Hemoglobin genes (normal variant as a result
of SNP)
6 CTC GAG glu
HbA 1 2 3 4 5 DNA CAC GTG
GAC TGA GGA RNA GUG CAC CUG ACU CCU AAs
val his leu thr pro
HbS 1 2 3 4 5 DNA CAC GTG
GAC TGA GGA RNA GUG CAC CUG ACU CCU
AAs val his leu thr pro
6 CAC GUG val
40
Hemoglobin genes (normal variant as a result
of SNP)
HbA 1 2 3 4 5 DNA CAC GTG
GAC TGA GGA RNA GUG CAC CUG ACU CCU AAs
val his leu thr pro
6 CTC GAG glu
HbC 1 2 3 4 5 DNA CAC GTG
GAC TGA GGA RNA GUG CAC CUG ACU CCU
AAs val his leu thr pro
6 TTC AAG lys
41
SNP Single Nucleotide Polymorphism(s)
A single nucleotide change within a
gene, sometimes referred to as a
benign mutation or a normal variant.
Such changes have been most characterized in
connection with enzyme activity (such as the
cytochrome p450 system) alterations.
42
Silent Mutation
Amino Acid Cys Leu Gly His
DNA code ACA GAC CCC GTG
Amino Acid Cys Leu Gly His
DNA code ACA GAC CCG GTG
A single base change occurs, but does not change
the amino acid sequence.
43
Missense Mutation
Amino Acid Cys Leu Gly His
DNA code ACA GAC CCC GTG
Amino Acid Trp Asp Gly His
DNA code ACC GAC CCC GTG
A single base change causes a different amino
acid to be placed with the protein.
44
Nonsense Mutation
Amino Acid Cys Leu Gly His
DNA code ACA GAC CCC GTG
Amino Acid Stop Leu Gly His
DNA code ACT GAC CCC GTG
A single base change occurs, and the resulting
change is a stop signal.
45
Frameshift Mutation
Addition or deletion of one base, always alters
amino acid position, disrupts reading frame and
protein synthesis
46
THE BIG DOG ATE THE CAT
THB IGD OGA TET HEC AT
THE PBI GDO GAT ETH ECA T