2Genes encode for
proteins and RNA
3Central Dogma of Biology
DNA -> RNA -> Protein
4In prokaryotes transcription and translation are
Coupled and found in the cytosol
5In Eukaryotes transcription occurs in
nucleus
6In Eukaryotes translation occurs in
cytoplasm or Rough ER
7prokaryotic gene expression
No mRNA processing and mRNA is polycistronic
8polycistronic
mRNA codes for more than one protein. Found mainly in Prokaryotes.
9Eukaryotic gene expression
monocistronic mRNA and mRNA processing
10monocistronic
This means mRNA only codes for one polypeptide.
11Insulin gene on chromosome 11
Only one strand is written but it is still a double helix
12Steps of Insulin gene expression
DNA-> coding strands-> templete strand-> transcript RNA-> adypeptide
13Types of RNA
Translated and nontranslated
15mRNA is used for
protein synthesis
16Non translated meaning
Not made into a protein
17non translated RNA
tRNA and rRNA
18tRNA
transfer RNA; type of RNA that carries amino acids to the ribosome
19rRNA
ribosomal RNA; type of RNA that makes up part of the ribosome
20snRNA
small nuclear RNA, spliceosome
21miRNA and siRNA
micro/small interfering RNA; binds to mRNA or DNA to block it, regulate gene expression, or cut it up
22Genes are part of
The human genome
23The human genome has _____ pairs
3 billion
24The human genome is ___ long
2 meters
25How much of the human genome is transcribed into RNA?
76%
26Transcription Signals
Promoter, transcribed region, terminator, regulatory sequences
27Promoter
specific region of a gene where RNA polymerase can bind and begin transcription
28transcribed region
the region of DNA that gets copied to RNA
29Terminator
Marks the end of a gene.
30regulatory sequence
controls gene expression
31What Synthesizes RNA
RNA polymerase
32RNA synthesis
DNA is used as a templete, Primer not required, rNTP is added to 3OH'
33rNTP
ribonucleoside triphosphate
34rNTP examples
RATp, rUTP, rGTP, rCTP
35Transcription steps
initiation, elongation, termination
36initiation of transcription
1. Recognition of the promoter or sigma factor(Bacteria)
2. RNA polymerase is recruited by sigma factor
3. RNA polymerase separates the DNA strands to form an open complex
373 common features of eukaryotic promoters
1. TATA box
2. +1 site
3. Regulatory/ response element
38TATA box
2 base pairs upstream from transcriptional start site. Determines precise starting point for transcription
39+1 site
where transcription begins
40Regulator / response element
Increases or decreases gene expression
41Eukaryotic pre initiation complex
RNA polymerase II & 5 different general transcription factors
42general transcription factors (GTFs)
Has the same job as the sigma factor
43Elongation Transcription
RNA polymerase synthesizes RNA 5' to 3'
44Templete strand
provides a templete for ordering a sequence of complementary bases in an RNA transcript
45Coding strand
the strand of DNA that is not used for transcription and is identical in sequence to mRNA, except it contains uracil instead of thymine
46termination of transcription
RNA polymerase reaches terminator sequence
47Direction of transcription ____
Varies
49post-transcriptional modification
the modifications that occur to an mRNA transcript before it is exported from the nucleus as mature mRNA. Include: splicing of introns, addition of 5' cap, addition of poly-A-tail and rearranging of exons
50Pre mRNA is capped
1. 7 methylguanosine is added to 5' end of pre mRNA
2. Amino acids in mRNA exit nucleus
3. Binding site for ribosome
4, prevents degradation
51poly-A tail
Added to 3' end, not encoded in DNA, aids in exit from nucleons, and prevents degradation
52RNA splicing
removes introns and joins exons, creating an mRNA molecule with a continuous coding sequence
53Introns
Noncoding segments of nucleic acid that lie between coding sequences.
55Alternative splicing
Can result in different proteins made from same DNA gene
56What catalyzes splicing events?
Splicesome
57Proteins are composed of
Amino acids
58Amino acids are joined together by
Peptide bonds
59Proteins have 4 levels of structure
primary, secondary, tertiary, quaternary
60primary protein structure
sequence of amino acids
61Secondary protein structure
coiling or folding of a polypeptide due to H-bonding between amino acids
62Tertiary protein structure
3D folding pattern of a protein due to side chain interactions
63quartnary structure of protein
When protein subunits combine
64Codon
three-nucleotide sequence on messenger RNA that codes for a single amino acid
67mRNA encodes for proteins at
The ribosome binding site(RBS)
68Start codon is located
Downstream from RBS
69Molecular machinery of translation
MRNA, ribosomes, tRNA, & translation factors
70translation factors
proteins needed for the three stages of translation
71tRNA helps
Decode messages on RNA
72tRNA structure
secondary structure, cloverleaf form, anticodon
73Anticodon
group of three bases on a tRNA molecule that are complementary to an mRNA codon
74aminoacyl-tRNA synthetase
An enzyme that joins each amino acid to the appropriate tRNA on the 3' end
75When tRNA is charged,
Energy is required
76Ribosomes that synthesize proteins are composed of
Protein and rRNA, small and large subunits
77ribosomes for Translation form in
Nucelous
783 sites in ribosome
A site, P site, E site
79A site
Amino-acyl tRNA site; the site on a ribosome where a new amino acid is added to a growing peptide.
80P site
holds the tRNA that carries the growing polypeptide chain
81E site
the exit site, where discharged tRNAs leave the ribosome
823 phases of translation
initiation, elongation, termination
83initiation of translation
1. Initiation factors bind small subunit to mRNA and RBS or Shine-Dalgarno sequence(Bacteria)
2. TFs recruit initiator rNA(tRNA met) to p site
3. Large and small subunits are associated
4. GTP hydrolysis provides energy for synthesis
84Elongation of translation
1. Ribosome trans locate with mRNA
2. Moves on codon down the message
3. Incoming tRNA binds to codon in A site
4. Uncharged tRNA leaves via E site
5. Elongation factors and GTP hydrolysis help
85termination of translation
occurs when a stop codon in the mRNA reaches the A site of the ribosome & release factors are used
86cotranslational sorting
the sorting process in which the synthesis of certain eukaryotic proteins begins in the cytosol and then halts temporarily until the ribosome has become bound to the ER membrane
87ER sequence
a sequence of about 6-12 amino acids that are predominantly hydrophobic and usually located near the N-terminus
88Muatation
A heritable change in genetic material
89Mutation is a source of ___ for natrual selection
variation
90new mutations are more likely to be
harmful than helpful
91Cancer
A disease caused by genetic mutations
92Point mutation
a genetic mutation where one nucleotide is changed
93point mutation types
substitution and addition/deletion
94Base subsitution effects
silent, missense, or nonsense
95effect of adding or deleting a base
frameshift
97missence
change in one amnio acid
98nonsense
chnage in a normal codon to a stop codon
99frameshift
produces a different amino acid sequence
100affected areas outside coding sequences
promoter, transcriptional regulatory element, splice sites, translational regulatory element, and intergonic region
101promoter mutation
may increase or decrease rate of transcription
102transcriptional regulatory element mutation
may alter the regulation of transcription
103splice sites mutation
may alter ability of pre-mRNA to be properly sliced
104translational regulatory element mutation
may alter the ability of mRNA to be translationaly regulated
105Intergonic region mutation
not as likely to have an effect on gene expression
106Sickle Cell disease
missence mutation in the HBB gene that encodes B-globin, changes gultamic acid to valine, and sticks cells together causing sickle shape
107What determines how severe and heritable a mutation is
Time and location
108gem-line cells
passes mutations on to offspring through half of gametes, occurs in sperm/egg cell or gamete progenitor
109somatic cells
body cells in which mutations occur during late development and are not passed down through gametes
110Sponatenous mutation
muations that occur because of abonormal biological processes
111Spontateous mutation causes
1. error in DNA replication 2. toxic metabolic products/free radicals 3. changes in nucleotide structure, and insertion pf transposons
112transposons
small segments of DNA that can insert at various sites in the genome
113induced mutations
caused by mutagens
114mutagens
components of the envionment, food, or cells that can cause mutation
115mutagen examples
radiation, chemicals, infectious agents, and cellular response
116Two components of DNA repair
deletion of damage and repair of damage
117Types of DNA repair:
Direct repair, nucleotide excision repair, and methyl directed mismatched reapir
118Direct repair
a repair enzyme recongizes incorrrect structure in the DNA and directly converts it back
119Nucelotide excision repair
portion od DNA strand containing an abonormal nucleotide is removed and replace
120Methyl directed mismatch repair
A Base pair mismatch is detcted and a strand of surrounding DNA is removed and replaced
121Cancer is characterized by
uncontrollable cell divison
122about ___% of cancers involve heritable genetic changes
10%
123most cancers about____ % do not involve hertiable genetic changes
90%
124slightly over ___ of human protein coding genes when mutated, can promote cancer
1%
125Benign
a tumor that stays in its original location
126metastasis
when the tumor spreads to other parts pf the body
127carcinogens
agents that increase the likelihood of devloping cancer
128___% of human cancers are related to exposure to carcinogens
80%
129Proto-oncogenes
a normal functioning gene that becomes an oncogene if mutated
130oncogenes
promotes cancer by keeping the cell divison signaling pathway in a permanent position
131Two functions of tumor supressor genes
maintain genome inegrity by by monitoring and repairing DNA damage & slows down and inhibits cell divison
132p53 tumor supression gene
turns on genes that repair DNa damage. If it is too severe, apoptosis is turned on
133RB tumor supression
inhibits the E2F activation gene for G1 to S phase cell cycle, prevents cell divison