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Transcript
Topics



Nucleic Acids: structure and function
 DNA
 RNA
Organization of the genome
Protein Synthesis (genetic expression)
 Transcription
 Translation
 Mutations
 Post-transcriptional modification
 epigenetics
DNA: Structure and Function
DNA Function
genetic
information
how to build, operate, and repair cell
Specifically how and when to make proteins
passed from one cell generation to the next;
from parent to child (gametes/sex cells)
From one cell to the next within an individual
DNA Structure
long
chains of nucleotides
Nucleotide = sugar + phosphate + nitrogenous base
Sugar = deoxyribose (5C)
4 Different Bases: A, T, G, C

Bases = pyrimidines (1 ring) or purines (2 rings)


sugar-phosphate backbone=covalent
base-base=hydrogen
hydrogen bond
3’
DNA Structure Cont.:
Double Helix
double stranded
5’
Twisted=helix
covalent bond
5’
3’
‘f’-five; ‘f’ phosphate; 5’ end
DNA Structure Cont.:
Complementary Base Pairing
4
different bases
Complementary pairing
C—G
A—T
Functional Characteristics of DNA: IMPORTANT!!
 Information
= order of the bases/base sequence
ATTGCGCA
Different sequencesdifferent meaning/info (proteins)
ATTGCGGA
Complementary
base pairing
Allows DNA to be copied over and over and
the information stays the same.
Importance of base-pairing
A
A
T
A
T
T
T
A
T
A
T
T
A
T
A
C
C
G
C
G
G
G
C
G
C
C
C
G
C
G
G
G
C
G
C
A
A
T
A
T
T
T
A
T
A
Importance of base-pairing continued
A
T
T
A
T
A T
T
A
A
T
A
T A
T
A
A
T
A
T A
C
G
G
C
G
C G
G
C
C
G
C
G C
C
G
G
C
G
C G
G
C
C
G
C
G C
A
T
T
A
T
A T
T
A
A
T
A
T A
DNA Organization
DNA
molecule = genes + regulatory DNA + “other”
“chromosome”
~3% of DNA
non-coding: ~97% of DNA
gene

=protein instructions
20-25k estimated genes (but >100,000 estimated proteins….problem…..)
regulatory

= when to activate gene/make a protein
e.g., transcription factors such as hormones can bind regulatory DNA
and signal a gene to be used
Regulates when
protein is made
(gene activated)
Protein building
instructions (gene)
DNA Organization
 DNA
is wrapped around histone (a protein)
 DNA + Histone = Chromatin
Chromatin
histone
3-31
DNA Organization: Histone and access
to genes
 Histone
is important in making genes accessible (usable) or
inaccesible (non-usable)
 If DNA can’t be accessesgene can’t be used (no protein)
 If DNA can be accessedgene can be used when needed
 Histone can control which/if genes can be used=Epigenetics
 acetylation allows access
 deacetylation shuts off/prevents access
 methylation prevents access/shuts off
 demethylation allows access/shuts off
 and others……….
Chromatin continued
Condensed chromatin:
transcription factors can’t get
to regulatory DNA to activate
gene use
acetylation and demethylation
Open/loose
structure allows
transcription
factors to
access DNA
and initiate
gene use
deacetylation
and methylation
and methylation
Condensed chromatin:
inaccessible
3-33
REPLICATION:
duplication of DNA as part of cell division
DNA Replication
 Happens
as part of cell cycle
 In preparation for cell division
 Duplicates all the DNA: 1 copy  2 copies
 One copy for each cell
 Semiconservative
G C
G C
G C
C G
C G
C G
G C
G C
G C
A T
A T
A T
T A
T A
T A
 Errors in replication  mutations (i.e. a change in genetic
information/DNA sequence)
1 copy of DNA
1 copy of
all DNA
2 copy of
All DNA
1 copy of DNA
Replication of DNA
Parent/mother cell
• Mitosis
divides/separate
daughter cells: the
each one
two copies
identical of
copy of all the
DNA: genetically identical
identical
to the mother cell
chromosomes
• Cytokinesis
divides up the
cytoplasm contents
DNA Replication
DNA
helicase “unzips” the DNA
New nucleotides are added/paired with the existing
strands
DNA polymerase binds the new nucleotides
together creating the P-S backbone
Result is two identical DNA molecules (i.e., the base
sequence is the same)
Genetic Expression
Proteins Synthesis:
how dna is used to make functional proteins
Genetic Expression: from DNA to cell function/structure
DNA  mRNA  Proteins  cell function/structure
•structure
•transport
•contraction
•receptors
•cell ID
•hormones/signaling
Protein Synthesis: making proteins from DNA
Transcription= DNA  mRNA (in nucleus)
2. Translation = mRNA  Protein (in cytoplasm @
ribosome)
1.
Nucleic Acids - RNA




Single stranded chains of nucleotides
Sugar = ribose
Bases and Pairing
 G, C, A, U replaces T
 G-C
 T-A or A (dna) –U (rna)
types of RNA (made from DNA):
 Messenger RNA – mRNA
 Transfer RNA – tRNA
 Ribosomal RNA – rRNA
 others (siRNA, miRNA, RNA based enzymes, etc)
2-59
Transcription:
from DNA  mRNA
 Transcription
Begins:
 When Transcription factors (e.g., hormones) bind DNA
transcripition starts/is initiated
 RNA polymerase binds to a “start” sequence/codon & unzips
DNA

promoter = how much transcription
 RNA
Polymerase moves down template strand
 complimentary RNA bases bind DNA
 RNA nucleotides bind together (via RNA poly)
 at end of gene mRNA detaches and RNA poly detaches
 DNA zips up when transcription is done
 Post-transcriptional
modification
3-35
Transcription
Template strand
Coding strand
3-36
Transcription
mRNA: a copy of the information on a gene



Created by transcription
Single strand of nucleotides
 Phosphate, ribose sugar, bases
 U instead of T
Codons = 3-base groups
One codon is a “start” codon
 Three codons are “stop codons”
 Each of the remaining 60 codons corresponds to an amino acid

tRNA




Single stranded piece of RNA
tRNA carries and delivers amino
acids to mRNA/ribosome
tRNA anticodon binds to mRNA
codon
 complementary
Each tRNA carries a specific amino
acid that corresponds to its
anticodon
3-44
Protein Synthesis and the Genetic Code
DNA template strand
3-43
Mutations, DNA, and Protiens
Mutation
= change in DNA base sequence
change in protien  change in structure and/or
function
Basic Types of Mutations
Point
mutations
substitution
insertion
frame-shift mutations
deletion
Point Mutations
 Substitution:
 ATT
GCG AGT TAT CCG
 ATT GCG AGT TAG CCG
 Insertion:
 ATT GCG AGT TAT CCG
 ATT GCG TAG TTA TCC G
 Deletion
 ATT GCG AGT TAT CCG
 ATT GCG GTT ATC CG
A
frameshifts
Base Sequences and Human Variation
 SNP’s
(single nucleotide polymorphisms)
 single nucleotide differences in the DNA between different
individuals
 responsible for most differences in appearance and physiology






ATT GCG ATC CGA TAT TTT AAC CCC ATA CGG TAT TTT TCG
ATT GCG TTC CGA TAT TTT AAC CCC ATA CGG TAT TTT TCG
ATT GCG ATC CGA TAT TTG AAC CCC ATA CGG TAT TTT TCG
ATT GCC ATC CGA TAT TTT AAC CCC ATA CGG TAA TTT TCG
ATT GCC ATC CGA TAT TTT CAC CCC ATA CGG TAT TTT TCG
ATT GCG ATC CGA TAT TTT CAC CCC ATA CGG TAA TTT TCG
RNA Synthesis & Post-transciptional Modification
Human
genome has <25,000 genes
Yet produces >100,000 different proteins
1 gene codes for an average of 3 different proteins
Accomplished by alternative splicing of exons
 This allows a given gene to produce several
different mRNAs
3-39
Post-transcriptional Modifcation
non-coding introns removed from mRNA
 Coding exons spliced together to make the mRNA that
will be used in translation
 multiple splicing patterns for each “pre-mRNA”
 1 gene  multiple mRNA/proteins

3-38
Alternative Splicing of mRNA:
one gene  two proteins
introns
From one gene
exons
Two types of
protein
Alternative Splicing of mRNA:
one gene  3 proteins
From one gene
Three types of
protein
Epigenetics






Changes in genetic expression that do not involve changes in base
sequences (gene and regulatory DNA has not been altered)
Changes in expression are due to changes in histone.
Genes can be “turned off” or “allowed to be accessed”
 Gene silencing (i.e., preventing gene use by making them inaccessible)
can be cause by (but is not limited to):
 Acetylation/deacetylation
 Methylation/demethylation
These changes can be copied and transferred/inherited from generation to
generation
Can contribute to diseases such as cancer, fragile X syndrome, and lupus
Identical twins can have differences in gene expression
 --because of epigenetic changes in response to differences in their
environments
3-74
acetyl, methyl, ubiquitin,
phosphate, S.U.M.O
DNA (genetics)  characteristics/physiology
DNA + environment = phenotype (characteristics)