Nucleic Acids: structure and function

1
Topics

• Nucleic Acids structure and function
• DNA
• RNA
• Organization of the genome
• Protein Synthesis (genetic expression)
• Transcription
• Translation
• Mutations
• Post-transcriptional modification
• epigenetics

2

• DNA Structure and Function

3
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

4
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)

5
DNA Structure Cont.Double Helix
hydrogen bond

• double stranded
• sugar-phosphate backbonecovalent
• base-basehydrogen
• Twistedhelix

covalent bond
f-five f phosphate 5 end
6
DNA Structure Cont.Complementary Base Pairing

• 4 different bases
• Complementary pairing
• CG
• AT

7
Functional Characteristics of DNA IMPORTANT!!

• Information order of the bases/base sequence
• ATTGCGCA
• ATTGCGGA
• Complementary base pairing
• Allows DNA to be copied over and over and the
  information stays the same.

Different sequences?different meaning/info
(proteins)
8
Importance of base-pairing
9
Importance of base-pairing continued
10
DNA Organization

• DNA molecule genes regulatory DNA other
• gene protein instructions
• 20-25k estimated genes (but gt100,000 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

chromosome
3 of DNA
non-coding 97 of DNA
Regulates when protein is made (gene activated)
Protein building instructions (gene)
11
DNA Organization

• DNA is wrapped around histone (a protein)
• DNA Histone Chromatin

Chromatin
histone
3-31
12
DNA Organization Histone and access to genes

• Histone is important in making genes accessible
  (usable) or inaccesible (non-usable)
• If DNA cant be accesses?gene cant be used (no
  protein)
• If DNA can be accessed?gene can be used when
  needed
• Histone can control which/if genes can be
  usedEpigenetics
• acetylation allows access
• deacetylation shuts off/prevents access
• methylation prevents access/shuts off
• demethylation allows access/shuts off
• and others.

13
Chromatin continued
Condensed chromatin transcription factors cant
get to regulatory DNA to activate gene use
acetylation and demethylation
Open/loose structure allows transcription factors
to access DNA and initiate gene use
and methylation
deacetylation and methylation
Condensed chromatin inaccessible
3-33
14
REPLICATION duplication of DNA as part of cell
division
15
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
• Errors in replication ? mutations (i.e. a change
  in genetic information/DNA sequence)

16
1 copy of DNA
1 copy of all DNA
2 copy of All DNA
1 copy of DNA
Replication of DNA

• Mitosis divides/separate the two copies of
  identical chromosomes
• Cytokinesis divides up the cytoplasm contents

Parent/mother cell
daughter cells each one identical copy of all
the DNA genetically identical to the mother cell
17
(No Transcript)
18
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)

19
(No Transcript)
20
Genetic ExpressionProteins Synthesishow dna
is used to make functional proteins
21
Genetic Expression from DNA to cell
function/structure

• DNA ? mRNA ? Proteins ? cell function/structure

• structure
• transport
• contraction
• receptors
• cell ID
• hormones/signaling

22
Protein Synthesis making proteins from DNA

1. Transcription DNA ? mRNA (in nucleus)
2. Translation mRNA ? Protein (in cytoplasm _at_
   ribosome)

23
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
24
Transcriptionfrom 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
25
Transcription
Template strand
Coding strand
3-36
26
Transcription
27
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

28
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
29
(No Transcript)
30
(No Transcript)
31
(No Transcript)
32
(No Transcript)
33
Protein Synthesis and the Genetic Code
DNA template strand
3-43
34
Mutations, DNA, and Protiens

• Mutation change in DNA base sequence
• change in protien ? change in structure and/or
  function

35
Basic Types of Mutations

• Point mutations
• substitution
• insertion
• deletion

frame-shift mutations
36
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
37
Base Sequences and Human Variation

• SNPs (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

38
RNA Synthesis Post-transciptional Modification

• Human genome has lt25,000 genes
• Yet produces gt100,000 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
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
40

• Alternative Splicing of mRNA
• one gene ? two proteins

introns
From one gene
exons
Two types of protein
41
Alternative Splicing of mRNAone gene ? 3
proteins
From one gene
Three types of protein
42
(No Transcript)
43
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
44
acetyl, methyl, ubiquitin, phosphate, S.U.M.O
45
DNA (genetics) ? characteristics/physiology

• DNA environment phenotype (characteristics)