Lecture 34 DNA Repair and How mutations occur Flashcards
1
Q
what are the types of genetic diseases?
A
- chromosome disorders
- single gene disorders
- multifactoral or complex
- sex linked and mitochondrial
2
Q
Chromosome disorders
A
- most common disease
- rearrangements/ translocations
- deletions
- insertions
- duplications
3
Q
Single gene disorders
A
- best characterized (several thousand)
- Dominant
- Recessive
- Codominant
4
Q
Multifactorial or complex
A
- Multiple genes
- gene-environment
5
Q
Sex linked and mitochondrial
A
- small genome that encodes for proteins
6
Q
What are the general categories of mutations
A
- somatic
- germline
7
Q
Are somatic mutations inheritable?
A
- no
- they arise other than gametes
- ex: cigarette smoking an lung cancer, p53 mutations
8
Q
Are germline mutations inherited?
A
- yes
- 12,000 + entries in OMIM currently
9
Q
What are the causes of mutations?
A
- spontaneous and induced
10
Q
What mutations arise naturally during DNA replication (mitosis) or during meiosis?
A
- spontaneous
11
Q
What type of mutations arise from radiation or chemicals?
A
- induced
12
Q
What are the types of mutations?
A
- silent
- missense
- Nonsense
- Transition
- Transverse
- Deletion
- Insertion
13
Q
Silent
A
- no change
- nucleotide change but resulting amino acid is the same
14
Q
Missense
A
- single amino acid change
15
Q
Nonsense
A
- stop codon produced and Truncated protein
- could have stop codon eliminated and get long protein
16
Q
Transition
A
- Pur/Pur
- Pyr/Pyr
17
Q
Transversion
A
- Purine/ Pyrimidine
18
Q
Deletion or insertion
A
- extra or missing amino avids
19
Q
Frameshift
A
- altered protein
- phasing that mRNA is read is shifted
20
Q
Other types of mutations through regulatory elements
A
- all these regulatory elements can be mutated
- promoter/enhancer - nuclear receptors
- splice site
- expanded repeat
- transposons
21
Q
What mutation is associated with huntingtons disease?
A
- expanded repeat
22
Q
Transposons
A
- mobile regulatory elements that jump around
23
Q
What mutation results in a different amino acid that is encoded?
A
- missense (1 base 1 amino acid)
24
Q
What goes into the nomenclature of mutations?
A
- amino acid designations
- genomic (gDNA) vas mRNA(cDNA) vs proteins
- coordinates
- substitutions that took place
25
What are alleles?
- sequence variants of a gene
26
How many alleles of each autosomal gene from your mother and father do you recieve?
- one
27
What chromosomes do females inherit
XX
28
What chromosomes do males inherit
XY
29
What are single nucleotide polymorphisms?
- single base differences at a specific position in the genome
30
Can SNPs occurring within a gene give rise to an allele
- Yes
31
How many SNPs are in the genome?
- hundreds of thousands of SNPs in the genome
| - walking mutation
32
Why are SNPs helpful to us?
- they give us land marks at nucleotide (crack) level
33
Are most of the spontaneous changes that happen in DNA eternal?
- no they are temporary because our body corrects them through DNA repair
34
What are some factors that can cause random changes?
- heat
- metabolic accidents
- radiation of various sorts
- exposure to substances in the environment
(only a few of these actually accumulate as mutations in DNA sequence)
35
fewer than 1 in ____ accidental base changes in DNA results in a permanent mutation
- 1000
36
How do we know that DNA repair is important?
- it is evident from the large investment that cells make in DNA enzymes or DNA repair proteins.
37
What happens when you have inactivation of DNA repair gene?
- increased rate of mutation and can lead to cell death or disease
38
Which is more stable, DNA or RNA?
DNA
39
how often is there sponaneous deamination of cytosine to uracil in DNA?
- rate of about 100 bases per cell per day
40
How much DNA of each human cell is lost daily?
- 5000 purine bases per cell due to their deoxyribose hydrolyzation of N-glycosyl
41
Depurination
- hydrolyzation of N-glycosly linkages
42
What are DNA bases also occasionally damaged by?
- an encounter with reactive metabolites produced in the cell ( including reactive forms of oxygen, H2o2, -OH, and -O2)
- exposure to chemicals in the environment
- UV radiation from sun can produce a covalent linkage between two adjacent pyrimidine bases in DNA to form thymine dimers
43
Hydrolytic attack
- deamination and , most frequent chemical reactions
44
What happens when you deaminate adenine?
- you get hypoxanthine
45
What happens when you deaminate guanine?
- you get xanthine
46
What happens when you deaminate cytosine?
- you get uracil
47
Can you deaminate thymine?
- No it doesnt have an amine group
48
Would a 5 methyl cytosine changing to thymine be considered natural or unnatural?
- natural
49
The spontaneous deamination products of A and G are recognized as unnatural when they occur in DNA and thus are readily recognized and repaired
- deamination of DNA nucleotides
50
Base excision repair
unnatural bases are recognized and removed by a specific DNA glycoslylase
51
Deamination and depurination
- hydrolytic reactions are the two most frequent spontaneous chemical reactions know to create serious DNA damage in cells
52
Deamination
- cytosine to uracil in DNA is estimated to occur at a rate of 100 bases per genome per day
53
Depurination
- lose 5000 purine bases A or G per day in each cell due to thermal disruption of their N-glycosyl linkages to deoxyribose
- this adenine or guanine is gone
54
Pyrimidine (C or T) dimer formation
- covalent linkage of two adjacent pyrimidines by UV light from the sun
55
What do pyrimidine dimers do?
- alter the structure of DNA and consequently inhibit polymerases and arrest replication
56
can dimers be repaired?
- they might be repaired by photo reactivation or nucleotide excision repair, but unrepaired dimers are mutagenic
57
Deamination Leads to
- DNA substitution (point mutation)
58
In the case of depurination leads to?
- DNA deletion
59
Do deamination and depurination change both strands?
- no one strand remains unchanged
60
How do nucleotide excision repair work?
- remove large chunk of DNA next to pyrimidine dimer and then DNA polymerase and DNA ligase add new chunk
- end up exactly like parental strand
61
Quick and dirty solution
- non homologous end joining
| - DNA scars
62
Homologous recombination
-delays progression of G1 to S phase and from S to M phase (through G2) in the cell cycle
63
same allele
homozygous
64
different allele
heterozygous
65
Principle of segregation
- sexually reproducing organisms possess genes that occur in pairs and that only one member of this pair is transmitted to the offspring
- one copy from dad and one from mom
66
Principle of independent assortment
- genes at differ loci are transmitted independently
| - genetic info is scrambled
67
What is homologous recombination?
- genetic exchange between a pair of homologous DNA sequences
- DNA breaks often occur from radiation damage or reactive chemicals
- DNA breaks also arise from DNA replication forks that become stalled or broken
68
Homologous recombination is a mechanism to
- accurately repair double strand DNA breaks
- exchange bits of genetic information
- assures accurate chromosome segregation during meiosis
69
Repair of broken replication fork can lead to
- exchange of DNA information
70
What drives homologous recombination?
- DNA base pairing
71
What happens when you separate DNA into single stranded molecules in test tube?
- DNA will spontaneous reform into double stranded DNA
| - proteins bind to DNA and hold it into open configuration for synthesis
72
Inadvertent joining of two segments of DNA from different chromosomes results in?
- inadvertent translocations
73
What proteins are involved in DNA repair?
- the enzymes. catalyzing repair are present at high concentrations in the nucleus
- number of accessory proteins are involved in control of repair
- loss of essential proteins needed for repair are generally lethal events
- Loss or alterations (mutations) of accessary proteins often leads to cancer
74
When do holliday junctions form?
- during homologous recombination
75
What are holiday junctions?
- two DNA strands switch partners between two double helices
76
Can somatic tissues give rise to cancer?
- yes despite them not being inherited
77
What measures how frequently chromosomes cross over?
- centemorgan
