Molecular Biology Flashcards
(214 cards)
1
Q
What are DNA and RNA short for?
A
◦ deoxyribonucleic acid
◦ ribonucleic acid
2
Q
What are examples of nucleic acids?
A
Both DNA and RNA b/c they are found in the nucleus and possess many acidic phosphate groups
3
Q
What are the building blocks of DNA?
A
deoxyribonucleoside 5’ triphosphate (dNTP, where N represents one of the four basic nucleosides)
4
Q
What are the five dNTPs?
A
◦ dATP
◦ dTTP
◦ dGTP
◦ dCTP
◦ dUTP
5
Q
What are nucleotides composed of?
A
They are built from three components:
1. A sugar (deoxyribose for DNA, ribose for RNA)
2. An aromatic nitrogenous base
3. 1-3 phosphate groups
6
Q
What are purines?
A
The bases guanine (G) and adenine (A)
7
Q
What are pyrimidines?
A
The bases cytosine (C), thymine (T), and uracil (U)
◦ pyramids (pyrimidines) have sharp edges, so they CUT
8
Q
What are nucleosides?
A
A ribose or deoxyribose with a purine or pyrimidine linked to the 1’ carbon
9
Q
What are nucleotides?
A
Phosphate esters of nucleosides, with one, two, or three phosphate groups joined to the ribose ring by the 5’ hydroxy group
10
Q
What are nucleoside triphosphates?
A
When nucleotides contain three phosphate residues
◦ abbreviated NTP (if the sugar is deoxyribose, they are abbreviated dNTP)
11
Q
What is considered the ‘backbone’ of DNA?
A
The sugar and phosphate portion of the nucleotide b/c that region doesn’t vary (the variable portion is the base)
12
Q
Nucleotides in the DNA chain are linked by what?
A
They are covalently linked by phosphodiester bonds b/w the 3’ hydroxy group of one deoxyribose and the 5’ phosphate group of the next deoxyribose
13
Q
What is an oligonucleotide?
A
A polymer of several nucleotides linked together
14
Q
What is a polynucleotide?
A
A polymer of many nucleotides
15
Q
How do you write out a polynucleotide?
A
Start at the 5’ end and continue to the 3’ end
16
Q
What does the Watson-Crick model tell us?
A
That cellular DNA is a right-handed double helix held together by hydrogen bonds between bases
17
Q
In the cell, how does DNA exist?
A
◦ In the nucleus, as a double-stranded polynucleotide
◦ w/ ds-DNA, the two long polynucleotide chains are hydrogen-bonded together in an antiparallel orientation
18
Q
How are the ds-DNA strands bonded together?
A
w/ hydrogen bonds b/w bases on adjacent chains
◦ A is always bound to T
◦ G is always bound to C
◦ Therefore, a H-bonded pair is always b/w a purine and a pyrimidine (therefore both pairs AT and GC take up the same amount of space)
19
Q
How many bonds are required for each pair
A
◦ GC has 3 H-bonds
◦ AT has 2 H-bonds
20
Q
How long is a kilobase pair?
A
A kbp is 1000 nucleotides long
21
Q
What is hybridization?
A
The binding of two complementary strands of DNA, into a double-stranded structure
◦ Also known as ‘annealing’
22
Q
What is denaturation?
A
The seperation of a double-stranded structure
◦ Also know as ‘melting’
23
Q
What is Chargoff’s rule?
A
◦ A = T & G = C
◦ A + G = T + C
24
Q
What shape is DNA?
A
A coiled, double helix
25
What does it mean to be right-handed double helix?
In ds-DNA, the two hydrogen-bonded antiparallel DNA strands form a corkskrew in a clockwise motion, with the bases on the interior and the ribose/phosphate backbone on the exterior
26
What force stabilizes the double helix of DNA?
van der Waals interactions b/w the bases, which are stacked upon each other
27
What is a genome?
The total of an organism's genetic information
28
What are eukaryotic genomes composed of?
Several large pieces of linear ds-DNA (chromosomes)
29
How many chromosomes do humans have?
46 chromosomes (23 of which are inherited from each parent)
30
What are prokaryotic (bacterial) genomes composed of?
A single circular chromosome
31
What is the shape of viral genomes?
They may have linear or circular DNA or RNA
32
How many base pairs does the human genome consist of?
Over 10^9 base pairs
33
How many base pairs does the bacterial genome contain?
10^6 base pairs
34
Is there a direct correlation b/w genome size and evolutionary sophistication?
No, since the organism with the largest known genomes are amphibians
◦ Much of the size difference in higher eukaryotic genomes is the result of repetitive DNA that has no known function
35
Why is the DNA in the free coiled?
B/c if it remained as a simple double helix floating free in the cell, it would be very bulky and fragile
36
What mechanism do prokaryotes have for making their single circular chromosome more compact and sturdy?
An enzyme, DNA gyrase
37
DNA gyrase
An enzyme that uses the energy of ATP to twist the gigantic circular molecule
◦ Only found in prokaryotes, not eukaryotes
38
How does gyrase function?
By breaking the DNA and twisting the two sides of the circle around each other, where the resulting structure is a twisted circle that is composed of ds-DNA
39
What does 'supercoils' mean?
The twists created by DNA gyrase are called supercoils, as they are coils of a structure that is already coiled
40
Do eukaryotes have more or less DNA in their genome than prokaryotes?
Eukaryotes have more DNA in their genome than Prokaryotes, therefore they require denser packaging to fit within the cell
41
How do eukaryotes package their DNA more densly than prokaryotes?
Eukaryotic DBA us wrapped around histones, then form nucleosomes (DNA wrapped around an octamer of histones), which is then packaged away
42
What are histones?
Globular proteins that eurkaryotic DNA is wrapped around for dense packaging (looks like beads on a string)
43
What are nucleosomes?
Composed of DNA wrapped around an octamer of histones (a group of eight)
◦ The string b/w the beads is a ;ength of double-helical DNA called linked DNA and is bound by a single linker histone
44
What is chromatin?
Fully packed DNA, composed of closely stacked nucleosomes
45
Why stain chromomes with chemicals?
To look for patterns & morphology
◦ Condensed metaphase chromosomes are usually used as they are compact and easier to see
46
What happens when chromosomes are treated?
Distinct light and dark regions become visible
47
What is heterochromatin
The darker regions of chromosomes, which are less dense
◦ It is rich in repeats
48
What is euchromatin?
Lighter regions of the chromosome which are less dense
◦ Have higher transcription rates and therefore higher gene activity as the looser packing makes DNA accessible to enzymes and proteins
49
What can be used to determine the degree of DNA coiling or compactness for a chromosome?
Density - and the degree of DNA coiling and compactness is constant and heritable
50
What is a centromere?
The region of the chromsome to which spindle fibers attach during cell division.
◦ Made of heterochromatin and repetitive DNA sequences
51
What are kinetochores?
How method in which fibers attach to the chromosome via
◦ They are multiprotein complexws that act as anchor attachment sites for spindle fibers
52
Do other protein complexes (other than kinetochores) bind the centromere?
Yes - but after only after DNA replication, to keep sister chromatids attached to each other
53
Describe a chromosome
◦ Two p (short) arms
◦ Two q (long) arms
◦ The centromere position defines the ratio between the arms
54
Different types of centromere positions
◦ Metacentric
◦ Submetacentric
◦ Acrocentric
◦ Telocentric
55
What is metacentric?
A chromosome with the centromere position in the middle of the two arms
56
What is submetacentric?
A chromosome with the centromere positioned just off to one side
57
What is acrocentric?
A chromosome with the centromere positioned distinctly off to one side
58
What is telcentric?
A chromosome with the centromere positioned at the end of a set of arms (only has either q or p arms)
59
What is a chromatid?
The arm(s) of a chromosome
60
What are telomere?
The ends of linear chromosomes
◦ At the DNA level, these regions are distinguished by the presence of distinct nucleotide sequences repeated 50 to several hundred times
61
Describe the length and sequence of telomeres
The repeated unit is usually 6-8 base pairs long and guanine-rich
◦ Many vertebrates have the same repeat (5'-TTAGGG-3')
62
Are telomeres single or double stranded DNA?
Are composed of both single and double stranded DNA
63
Where is single-stranded DNA found on a telomere?
It is found at the very end of the chromosome and is about 300 base pairs in length
◦ It loops around to form a knot, held together by many telomere-associated proteins
64
What is the purpose of single-stranded DNA for telomeres?
It's knot form held together by telomere-associated proteins helps stabilize the end of the chromosome
◦ Specialized telomere cap proteins distinguish telomere from double-standed breaks and this prevents activation of repair pathways
65
What is the overall function of telomeres?
◦ To prevent chromosome deterioration and prevent fusion with neighbouring chromsomes
◦ They function as disposable buffers, blocking the ends of chromosomes
66
Do prokaryotes have/use telomeres
No - since most prokaryotes have circular genomes, their DNA does not contain telomeres
67
What number and combination of chromosomes does each humans have?
◦ 24 chromosomes (22 autosomes, plus 2 different sex chromosomes)
68
How many base pairs and number of genes does the human genome have
◦ 3.2 billion base pairs, which code for ~ 21 000 genes
69
What is the human genome composed of?
Regions of high transcription rates (coding DNA), and intergenic regions (non-coding DNA)
70
What are intergenic regions?
Composed of noncoding DNA
◦ They may direct the assembly of specific chromatin structures and can contribute to the regulation of nearby genes, but many have no known function
◦ Tandem repeats and transposons are major conponents of intergenic regions
71
What can be infered when a genomic region has high transcription rates?
That it is rich in genes
72
What is a gene?
A DNA sequence that encodes a gene product
◦ It includes both regulatory regions and a region that codes for either a protein or a non-coding RNA
73
What are examples of a regulatory region?
◦ Promoters
◦ Transcription stop sites
74
Is nucleotide variation across a genome common?
Yes, both small-scale and large-scale variation across a genome is common
75
What is the predicted rate of nucleotide variation in the human genome?
1 variation in every 1000 base pairs
76
What are variations in the human genome called?
Single nucleotide polymorphisms (SNPs) - essentially mutations
77
Where are SNPs most common?
They occur most frequently in noncoding regions of the genome, however some SNPs can lead to specific traits and phenotypes
78
What are copy number variations?
CNVs are structural variations in the genome that lead to different copies of DNA sections
79
To what degree can copy number increase or decrease?
◦ Large regions of the genome (10^3 to 10^6 base pairs) can be duplicated (increasing copy number) or deleted (decreasing copy number)
80
How do copy number variations occur?
◦ The specific mechanism is not known
◦ May be due to misalignment of repetitive DNA sequences during synapsis of homologous chromosomes in meiosis
81
Do CNVs or SNPs impact larger regions of the genome?
CNVs apply to much larger regions of the genome compared to SNPs (they are a normal part of our genome - 0.4% of the genome can have CNV, but have also been associated with cancer and diseases
82
What functions are often enriched in CNVs?
◦ Brain development and activity
◦ Immune system function
83
Is much of our genome single copy?
Yes - there is only one copy of the gene in a haploid set of the genome
◦ This is true for most eukaryotic genes that code for proteins
84
Are there regions of the genome that have tandem repeats?
Yes - the human genome have over a thousand regions of tandem repearts
85
What are tandem repeats?
Where short sequences of nucleotides are repeated one right after the other, from as little as 3 to over 100 times
◦ They often show variation in length between individual and therefore can be useful in DNA fingerprinting
86
Are repeats (in tandem repeats) stable or unstable?
Repeats can be unstable, when the repeating unit is short (such as di- or trinucleotides), or when the repeat itself is very long
87
What can happen the repeats in tandem repeats are unstable?
Can lead to chromosome breaks and some have been implicted in disease
88
Where in chromosomes can tandem repeats occur?
All of the following are rich in repeats
◦ Heterochromatin
◦ Centromeres
◦ Telomeres
89
What is the role of DNA?
DNA encodes and transmits the genetic informtion passed down from parents to offspring
90
Has DNA always been believed to carry genetic information?
No, prior to 1944 it was believed that protein carried genetic information, since protein have a 20 letter 'alphabet' (the amino acids), which DNA only has 4 letters (the four nucleotides)
91
How was DNA determined to carry genetic information?
In 1944, Oswald Avery showed that DNA was the active agent in bacterial transformation, meaning he proved tht pure DNA from one type of E. coli bacteria could transform E. coli of another type, causing it to acquire the genetic nature of the first type
92
What did Hershey and Chase proved in relation to DNA?
They proved that DNA was the active chemical in the infection of E. coli bacteria by bacteriophage T2
93
Does DNA directly exert its influence on cells?
No, it contains sequences of nucleotides known as genes that serve as templates for the production of another nucleic acid known as RNA
94
What is transcription?
The process of reading DNA and writing the information as RNA
95
What is the outcome of transcription?
It eithe generates a final gene product (as in the case of all non-coding RNAs), or it produced a messenger molecule
96
What happened when mRNA is produced?
Messanger RNA is read, and the information is used to construct protein
97
What is translation?
The synthesis of proteins using RNA as a template - and is accomplished by the ribosome
98
What is the ribosome?
A massive enzyme composed of many proteins and pieces of RNA (known as ribosomal RNA or rRNA)
99
What is the central dogma of molecular biology?
The fundamental law, outlining the unidirectional flow of DNA -> RNA -> Protein
◦ This is the mechanism whereby inherited information is used to create actual objects, namely enzymes and structural proteins
100
What is the genetic code?
The language used by DNA and mRNA to specify the building blocks of proteins
101
What is the alphabet of the genetic code?
◦ Consists of four letters: A, T, C, G
102
Transcription vs. translation
◦ To transcribe something is to listen and write it down as text (the message doesn't chnge nor does the language). Cellular transcription is the process whereby a code is read from a nucleic acid (DNA) and written in the langauge of another nucleic acid (RNA), so the language is the same
◦ To translate something is to change it from one language to another. Cellular translation, nucleic acids are read and polypeptides are written, so the language does change
103
What is the minimum codon size to specify 20 amino acids?
3 nucleotides
104
What is a codon?
A nucleic acid word (3 nucleotide letters)
105
How specific is each codon?
Very - each codon codes for a particular amino acid
106
In the genetic code, why is U (uracil) present and T (thymine) absent?
B/c RNA is the nucleic acid that actually encodes protein during translation, and RNA uses U instead of T
107
How many codons are there?
64
108
How many codon specify amino acids?
What is the purpose of those remaining?
◦ 61 codons specify amino acids
◦ 3 codons are 'stop codons'
109
What is the function of stop codons?
To notify the ribosome that the protein is complete and cause it to stop reading the mRNA
110
What are stop codons also refered to as, and why?
◦ Nonsense codons b/c they don't code for any amino acid
111
Does only one codon code for each amino acid?
No, most of the twenty amino acids can be coded for by more than one codon
◦ Often, all four of the codons with the same first two nucleotides encode the same amino acids
112
What are synonyms (in reference to codons)
They are two or more codons coding for the same amino acid
113
What does it mean that the genetic code is said to be degenerate?
This is b/c the genetic code has synonyms
114
Can each codon be specified by several amino acids?
No, although an amino acid can be specified by several codons, each codon specified only a single amino acid
◦ This means that each piece of DNA can be only interpreted in one way
115
Can the genetic code be ambiguious due to the degenerate nature of codons?
No, as each codon specified only a single amino acid - the code has no ambiguity
116
What aspects of molecular biology are not explicitly stated in the central dogma?
◦ Some viruses (retroviruses) make DNA from RNA using the enzyme reverse transcriptase
◦ Information can also be transferred in other ways. Ex. DNA methylation and post-translational modification of proteins can alter gene expression and convey information despite the fact that neither is directly included in the central dogma
◦ Many final gene products are not proteins but are RNAs instead
117
What is the control center of the cell?
The DNA genome
118
What is the outcome of mitosis?
It produced two identical daughter cells from one parental cell - each daughter must have the same genome as the parent.
◦ Therefore, cell division requires duplication of the DNA
119
What is required for cell division to occur?
Replication of the DNA (which is an enzymatic process)
120
When does DNA replication occur?
During the S (synthesis) phase in interphase of the cell cycle
121
What is the 'old' DNA strand called?
What is the 'new' DNA strand called?
◦ The old strand is the parental DNA
◦ The new strand is the daughter DNA
122
What is conservative replication?
The parental ds-DNA would remain as-is while as entirely new double-stranded genome was created
123
What is the dispersive replication theory?
That both copies of the genomes were composed of scattered pieces of new and old DNA
124
What is semi-conservative replication?
That after replication, one strand of the new double helix is parental (old) and one strand is newly synthesized daughter DNA
125
What are the key points of DNA replication?
1. DNA replication is semi-conservative
2. Polymerization occurs in the 5' to 3' direction
3. DNA pol requires a template
4. DNA pol requires a primer
5. Replication forks grow away from the origin in both directions (each replication fork contains a leading strand and a lagging strand)
6. Replication of the leading strand is continuous and leads into the replication fork, while replication of the lagging strand is discontinuous, resulting in Okazaki fragments
7. Eventually, all RNA primers are replaced by DNA, and the fragments are joined by an enzyme called DNA ligase
126
How is DNA replication semiconservative?
Individual strands of the double-stranded parent are pulled apart, and then a new daughter strand is synthesized using the parental DNA as a template to copy from. Each new daughter chain is perfectly complementary to its template or parent
127
What is the form of DNA when not being replicated?
It is tightly coiled
128
What needs to happen to DNA prior to replication being able to occur?
The double helix must be uncoiled, and separated into two single strands (this is done by the enzyme, helicase)
129
Would you expect helicase to use the energy of ATP hydrolysis to function?
Yes b/c separating the strands requires the breaking of many H-bonds
130
What protein is used to find the ORI in prokaryotes?
DnaA
131
What proteins in eukaryotes are used to find the ORI?
Three proteins are used in conjunction, two of which are synthesized during M and G1 phases of the cell cycle but rapidly destroyed once the S phase begins - this means these two proteins link DNA replication to the cell cycle, ensuring DNA replication doesn't initate during other phases of the cell cycle
132
What happens when helicase unwinds the helix at the origin of replication?
The helix gets wound more tightly upstream and downstream from this point
133
Function of topoisomerases
It is an enzyme that cuts one or both of the strands and unwaps the helix, releasing the excess tension created by the helicases (the chromosome would get tangled and eventually break w/out it)
134
Is ss-DNA more or less stable than ds-DNA?
ss-DNA is much less stable than ds-DNA
135
Function of single-strand binding proteins
SSBPs protect DNA that has been unpackaged in preparation for replication and help keep the strands separated
136
What is an open complex?
The separated strands created by SSBP - only in this state may replication now begin
137
What must be synthesized for each DNA template strand?
An RNA primer
138
How is an RNA primer synthesized?
The primosome is created by a set of proteins, of which the central component is an RNA polymerase called primase
◦ The RNA primer is usually 8-12 nucleotides long, and is later replaced by DNA
139
What is primase?
An RNA primer
140
Why is primer synthesis important in DNA replication?
Because the next enzume, DNA polymerase, cannot start a new DNA chain from scatch - it can only add nucleotides to an existing nucleotide chain
141
How is daughter DA created?
As a growing polymer
142
What is DNA polymerase
DNA pol catalyzes the elongation of the daughter stand using the parental template, and elongates the primer by adding dNTP's to its 3' end
143
What does the 3' hydroxyl group of dNTP's act as in DNA replication?
As a nucleophile in the polymerization reaction to displace 5' pyrophosphate for the dNTP to be added
144
In what direction is the template DNA strand read?
3' to 5'
145
What is DNA pol apart of?
A large complex of proteins called the replisome (other accessory proteins in this complex help DNA polymerase and allow it to polymerize DNA quickly
146
How many components does the prokaryotic replisome contain? The eukaryotic replisome?
◦ The prokaryotic replisome contains 13 proteins
◦ The eukaryotic, 27 proteins
147
Why does the eukaryotic replisome require additional components?
B/c its replication machinery must also unwind DNA from histone proteins
148
What happens once DNA pol attaches during DNA replication?
Rapid elongation of the daughter strand
149
Does DNA replication only happen on one strand at a time?
No - RNA primers attach on both strands, and since the two template strands are antiparallel, the two primers will elongate towards opposite ends of the chromosome
150
How/does DNA pol check its work?
Yes - DNA pol checks each new nucleotide to make sure it forms a correct base-pair before it is incorporated into the growing polymer
151
What is the thermodynamic driving force for the polymerization reaction?
The removal and hydrolysis if pyrophosphate (P2O7 4-) from each dNTP added to the chain
152
Is there ever 3' to 5' polymerization activity?
NEVER!
153
Can DNA pol start a new nucleotide chain on its own?
No - it requires a primer
154
In what diretion does DNA replication proceed?
In both directions, away from the origin of replication
155
In what direction are both DNA template strands read? In what direction are daughter strands elongated?
◦ Both template strands are read 3' to 5'
◦ Both daughter strands are elongated 5' to 3'
156
What are replication forks?
The areas where the parental double helix continues to unwind, with the leading replication strand moving towards the fork, while the lagging replication strand moves away from it
157
How does replication differ for DNA strands on opposite side of the ORI?
◦ The leading strand is elongated continuously, as the replication fork widens
◦ Once some of the top template chain is exposed, primase comes in and lays down a primer, which DNA pol can elongate
◦ These events are continuously repeated
158
What is the leading strand?
The strand of DNA that is continuously elongated into the widening replication fork
159
What is the lagging strand?
The stand during DNA replication that must wait until the replication fork widens before beginning to polymersize
160
What are Okazaki fragemtents?
Small chunks of DNA comprising the lagging strands
161
As the replication forks grow, does helicase have to continuously unwind the double helix and separate the strands?
Yes
162
What is DNA polymerase called (description) and why?
It is said to be processive b/c it rapidly builds DNA, is able to add tens of thousands of nucleotides before falling off the template
163
Do eukaryotes only use one or a few pol enzymes?
They have several different DNA pol enzymes, and their mechanism of action is complex
164
How many DNA pol enzymes do prokaryotes use?
◦ Five (DNA Pol I, II, III, IV, V
165
What is the function of DNA Pol III in prokaryotes?
◦ It is responsible for very fast and accurate elongation of the leading strand - it has hiught processivity
◦ It has 5' to 3' polymerase activity
◦ It has 3' to 5' exonuclease activity - therefore it has the ability to proofread its work and fix any mistakes
◦ It has no function in repair, so it is considered a replictive enzyme
166
What is an exonuclease?
An enzyme that cuts a nucleic acid chain at the end - this is when the enzyme moves backward to chop off the nucleotide it just added, if it was incorrect (acts as a proofreading function)
167
What is an endonuclease?
An enzyme that will cut a polynucleotide acid chain in the middle of the chain, usually at a particular sequence
168
What are two imporant type of endonucleases?
1. Repair enzymes
2. Restriction enzymes
169
What are repair enzymes?
A type of endonuclease that removes chemically damaged DNA from the chain
170
What are restriction enzymes?
A type of endonuclease that is found in bacteria, with the role of destroying the DNA of infecting viruses, thus restricting the host range of the virus
171
What is the function of DNA pol I in prokaryotes?
◦ It starts adding nucleotides at the RNA primer - this is 5' to 3' polymerase activity
◦ It also has 3' to 5' exonuclease activity (proofreading)
◦ DNA pol I removes the RNA primer via 5' to 3' exonuclease activity, wheen simultaneously leaving behind new DNA in 5' to 3' polyermase activity
◦ It is important for exision repair
172
Does DNA pol I or DNA pol III have higher processivity?
DNA pol III has better processivity, so it takes over from DNA pol I usually ~400 base pairs downstream of the ORI (b/c DNA pol I can only add about 15-20 nucleotides per second)
173
What is the function of DNA pol II in prokaryotes?
◦ It has 5' to 3' polymerase activity, and 3' to 5' exonuclease proofreading function
◦ It participates in DNA repair pathways and is used as a backup for DNA pol III
174
What is the function of DNA pol IV and DNA pol V in prokaryites?
◦ They have similar characteristics
◦ They are error prone in 5' to 3' polymerase activity, but function to stall other polymerase enzymes at replication forks when DNA repair pathways have been activated - this is an important part of the prokaryotic checkpoint pathway
175
Main characteristics of prokaryotic replication
◦ Only have one chromosome, which only has one ORI
◦ Circular chromosome, therefore makes a circle from a circle
◦ Replication is said to proceed via theta mechanism, and is refered to as theta replication
176
Main characteristics of eukaryotic replication
◦ Each chromoome has several origins, only having one would be too slow b/c their chromosomes are so large
◦ Replication refered to as making replication bubbles due to the many 'bubble' shapes made by replication forks
◦ Eventually the replication forks meet, and the many daughter strands are ligated together
177
What is a difficulty in DNA replication in eukaryotes nearing the end?
As DNA pol can only function in the 5' to 3' direction, and requires a primer, at chromosome ends, there will eventually be no spot on the lagging strand for a primer
◦ Therefore, DNA replication machinery is unable to replicate sequence at the ends of chromosomes and after each round of the cell cycle and DNA replication, the ends of the chromosomes shorten
178
What are telomeres?
Disposable repeats at the end of chromosomes - they are consumed and shorted during cell division, becoming 50-200 bp shorter
179
What happens when telomeres become too short?
They reach a critical length where the chromosome can no longer replicate
◦ This leads to cells being able to activate DNA repair pathways, enter a senescent state (where they are alive but no dividing), or activate apoptosis (programmed cell death)
180
What is the Hayflick limit?
The number of times a normal human cell type can divide until telomere length stops cell division
◦ Many age related diseases are linked to telomere shortening
181
What is telomerase?
An enzyme that adds repetitive nucleotide sequences to the ends of chromosomes and therefore lengthens telomeres
◦ It is a ribonucleoprotein complex, containing an RNA primer and reverse transcriptase enzyme
◦ The telomerase complex continjuously polymerizes, then translocates, allowing extension of six-nucleotide telomere repeats
182
What are reverse transcriptases?
Enzymes that read RNA templates and generate DNA
183
In most organisms, where is telomerase only expressed?
In the germ line, embryonic stem cells, and some white blood cells
184
What is the connection b/w telomeres and cancer
Telomerase can be expressed in cancer cells, which can help the cells immortalize
◦ Telomere extension allows the cells to bypass senescence and apoptosis, contributing to their transformation to a pre-cancerous state
185
Define genetic mutation
Any alteration of the DNA sequence of an organism's genome
◦ This can be inherited or acquired throughout life
186
What are germline mutations?
Mutations that can be passed onto offspring since they occur in the germ cells (which give rise to gametes)
187
What are somatic mutations?
They occur in somatic (non-gametic) cells and are not passed onto offspring
188
What are causes of mutations?
Most are induced by an environmental or chemical factor, but they can also occur spontaneously
◦ Physical mutatgens
◦ Reactive chemicals
◦ Biological agents
189
What are physical mutagens?
◦ Ionizing radiation (x-rays, alpha particles, and gamma rays)
◦ UV light causes photochemical damage to DNA
190
How does UV light cause photochemical damage to DNA?
Ex. If two pyrimidines (two C's or two T's) are beside each other on a DNA backbone, UV light can cause them to become covalently linked
◦ The formation of the pyrimidine dimers distorts the DNA backbone and can cause mutations during DNA replication if they are not repaired
191
Why is ionizing radiation dangerous?
Ionizing radiation (x-rays, alpha particles, and gamma rays) can cause DNA breaks
◦ If this only occurs on one strand, it can be easily repaired b/c the helix is still held together
◦ If this occurs on both strands, and the backbones are broken close to each other on a segment of DNA, a double-stranded break (DSB) occurs, which is hard to fix as the chromosome has been split into two pieces
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Why do reactive chemicals cause mutations?
B/c many chemicals either interact directly w/ DNA, or turn into damaging agents as they're being processed by a cell
◦ Chemicals can covalently alter bases, can cause cross-linking or strand breaks
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What are cross-links?
Abnormal covalent bonds between different parts of DNA
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What is a mutagen?
Any compound that can cause mutations
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How do chemicals cause mutations?
Compounds that look like purines/pyrimidines (have a large flat aromatic ring structure) cause mutations by inserting themselve b/w bp, or intercalculating, which causes errors in DNA replication
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What is an example of a mutagen?
Ethidium bromide
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How do biological mutations cause mutations?
Ex. Even though DNA pol has proofreading and correction abilities, it can still make a mistake. If mistakes are not corrected, it will be passed on to all daughter cells - in this cause there is no mutagen, the mistake is spontaneous.
◦ Viruses can also affect DNA, as lysogenic viruses insert into the genome of the host cell, and this can cause mutations and disrupt genetic functions. Due to this, some viruses can cause cancer. Additionally, transposons can induce mutations.
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What are the seven types of mutations?
1. Point mutations
2. Insertions
3. Deletions
4. Inversions
5. Amplifications
6. Translocations & rearrangments
7. Loss of heterozygosity
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What are point mutations?
Single base pair substitutions
◦ They can be transitions (substitution of a pryimidine for another pyrimidine, etc.) or transversions (substitution of a purine for a pyrimidine, etc)
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What are the three types of point mutations?
1. Missense mutation
2. Nonsense mutation
3. Silent mutation
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What is a missense mutation?
When one amino acid is replaced with a different amino acid
◦ This may not be serious if the amino acids are similar
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What is a nonsense mutation?
A stop codon replaces a regular codon and prematurely shortens the protein
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What is a silent mutation?
A codon id changed into a new codon for the same amino acid, so there is no change in the proteins amino acid sequence
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What is an insertion mutation?
The addition of one or more extra nucleotides into the DNA sequence
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What is a deletion mutation?
The removal of nucleotides from the sequence
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What are frameshift mutations?
Mutations that cause a change in the reading frame (insertions, deletions, transposons, etc - if you only add or delete. If you delete and then add the same number, will not result in a frameshift)
◦ Note that a frameshift can lead to premature termination of translation, creating an incomplete polypeptide if it results in the creation of an abnormal stop codon
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For each type of mutation, does it involve a change in the genotype, the phenotype, or both?
◦ All mutations involve a change in the genotype
◦ Most mutations also cause a change in the phenotyoe, but with conservative mutations, this can be hard to detect
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Are insertions/deletions always small scale or can they be large scale?
They can involve thousands of bases
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What is an inversion?
When a segment of a chromosome is reversed end to end. The chromosome undergoes breakage and rearragement with itself
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What can insertions, deletions and inversions be caused by?
Transposons
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What is chromosome amplification?
When a segment of a chromosome is duplicated
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What is translocation?
It is the result when recombination occurs b/w nonhomologous chromosomes
◦ This can create gene fusion, where a new gene product is made from parts of two genes that were not previously connected (this is often common in cancer)
◦ Translocations can be balanced (where no genetic information is lost), or unbalanced (where genetic information is lost or gained)
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What are transposons?
Transposable elements are mobile genetic elements in genomes
◦ Found in both prokayotes and eukaryotes
◦ Can cause mutations & chromosome changes like inversions, deletions, and rearrangements
◦ There are three common types, each with a different structure
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What are the three common types of transposons?
1. IS element
2. More complex
