DNA Repair & How Do Mutations Occur (Exam IV) Flashcards
Cellular synthesis of new daughter strands of DNA from a parental strand during the s phase of the cell cycle needed for cell division
DNA replication
Change in DNA sequence form a parental strand to a daughter strand
DNA mutation
Result in altered gene expression, splicing or altered proteins generated from the mutated DNA sequence
Functional DNA mutations
Division of the nucleus of eukaryotic cell, involving condensation of the DNA into visible chromosome & separation of the duplicated chromosome to form two identical sets
Mitosis
Special type of cell division that occurs in sexual reproduction & involves two successive nuclear divisions with only one round of DNA replication, thereby producing haploid cells from a diploid cell
Meiosis
Changes in the nucleotide sequence of a chromosomes that cause disease
Gene mutation responsible for disorders
List the single base pair substitutions that may or may not result in disorders (5):
Deletion
Insertion
Substitution
Silent
Missense
An identifiable segment of DNA sequence with a known physical location on a chromosomes & enough variation between individuals
Genetic marker
The inheritance & co-inheritance of alleles of a given gene in genetic markers can be:
Traced
Can help link an inherited disease with the responsible genes
Genetic markers
DNA segments close to eachother on a chromosome tend to be:
Inherited together
Used to track the inheritance of a nearby gene that has not yet been identified but whose approximate location is known
Genetic markers
Genetic markers are used in:
Linkage analysis
Variation between individuals in a population at specific nucleotides in their DNA sequence
Single nucleotide polymorphisms (SNPs)
DNA sequence variants of a gene
Alleles
Mechanism by which delaminated and depurinated nucleotides are repaired
Base excision repaur
Mechanism by which pyrimidine dimers are repaired
Nucleotide excision repair
Formed during homologous recombination which allows DNA strands to switch partners between two DNA double helices
Holiday junction
DNA is under constant pressure to ____ in its DNA sequence
Acquire changes
Most changes in DNA are repaired before they become
A stable part of DNA passed onto the daughter cells
When mutations occur in somatic tissues:
They CANNOT be inherited
Although mutations in somatic tissues CANNOT be inherited, they CAN:
Give rise to diseases such as cancer
When mutations arise in the DNA of gametes:
They will be passed on to the offspring
List the chromosome disorders that can cause genetic disease (5):
1- rearrangements
2- translocations
3- deletions
4- insertions
5- duplications
Single gene disorders can be (3):
Dominant
Recessive
Codominant
A ______ can give rise to disease
Single base pair change
Involve large chunks of DNA that get moved around
Chromosome disorders
Genetic diseases caused by multigenic or gene-environment interactions that can occur & contribute to the formation of a complex trait
Multifactorial or Complex disorders
Disorders that involve the X & Y chromosomes
Sex-linked
Mechanisms that cause mutations in the mitochondrial DNA & affect the genes they encode resulting in genetic disease
Mitochondrial disorders
Somatic mutations are ____ while germline mutations are ____
Non-inheritable
Inheritable
A mutation caused by cigarette smoking resulting in lung cancer would be categorized as:
Somatic mutation
A mutation in the p53 gene that typically would cause a form of cancer would be categorized as:
Somatic mutation
A mutation that affects the sperm or egg:
Germline mutation
Mutations that can be passed on to your children dependent upon the degree of the mutation
Germline mutation
Mutations that arise naturally during DNA replication (mitosis) or during meiosis
Spontaneous mutation
Mutations caused by exposure to environmental insults
Induced mutations
Environmental insults that cause can induced mutations include:
Radiation
Chemicals
A mutation in which the DNA sequence is altered but results in no change of amino acid
Silent mutation
A mutation that results in a single amino acid change
Missense mutation
A mutation resulting in a codon being products ultimately stopping translation & producing a truncated protein
Nonsense mutation
Nonsense mutations ultimately result in:
Truncated proteins
Mutations that disrupt the reading frame insertion or deletion of a base
Frameshift mutation
A mutation resulting in a glycine getting substituted for a valine would be a:
Missense mutation
The LRP5 mutation resulting in osteoporosis pseudoglioma syndrome producing truncated proteins is an example of:
Nonsense mutation
A purine getting exchanged for another purine or pyrimidine getting replaced by another pyrimidine is considered:
Transition mutation
A purine getting substituted for a pyrimidine (vice versa)
Transversion mutation
A type of mutation resulting in extra amino acids
Insertion
A type of mutation resulting in missing amino acids
Deletion
Maybe you have a single nucleotide deletion or insertion & because the mRNA reads every three nucleotides instead of it reading 1, 2, 3 its now reading 2, 3, 4 resulting in an altered protein- this is an example of:
Frameshift mutation
A Frameshift mutation typically results in the:
wrong amino acid being placed
Cystic fibrosis is due to a _____ mutation
3 base deletion of deltaF509 (phenylalanine)
List the types of mutations that don’t necessarily affect the protein being made but may affect the amount of or expression of the protein (4):
1- promotor/enhancers (nuclear receptors)
2- splice site
3- expanded repeat
4- transposons
Promotors & enhancers are
Nuclear receptors
Important for regulating the binding of a nuclear receptor to the DNA to tell that gene to be expressed or not expressed
Promotor
Mutating an important enhancer will:
Change the level of gene expression (amount of protein that gets made)
A class of sequencing elements found in DNA that are associated with the level of transcription & can be great distances from the start site of transcription
Enhancers
A mutation affecting the way the mRNA is spliced ultimately resulting in a protein with incorrect information in it
Splice site mutations
Where you would typically have a small repeat element of amino acids in DNA that gets exacerbated into a huge repeat element
Expanded repeat mutation
Huntington’s disease is caused by a ______ mutation
Expanded repeat
Mobile genetic elements that jump around in the genome & dependent upon where they are inserted can cause changes in gene expression
Transposons
Name the type of mutation
Silent
Name the type of mutation
Missense
Mutations can be designed by (nomenclature) (5):
1- amino acid change
2- position in genomic DNA
3- position in mRNA
4- position in cDNA
5- changes in the protein
Type of system is used in regards to nomenclature of mutations
Coordinate system
The mutation A1215T would mean:
Alanine at the position ____ in the protein is changed to a ____
1215; threonine
Single base pair differences at a specific position in the genome
SNPs
SNPs occurring within a gene can give rise to an:
Allele
How many SNPs are in the genome
Millions
We use SNPs to help identify where ______ might be located
Allele or trait causing mutations
Why do cells in our body need DNA repair
To have a mechanism to maintain genetic stability
Maintaining the genetic stability that an organism needs for survival requires not only an extremely accurate mechanism for ___________ but also mechanisms for repairing ___________ that occur continually in DNA
DNA replication
Accidental lesions
Most spontaneous changes in DNA are:
Temporary
Most spontaneous changes in DNA are temporary because:
They are immediately corrected through DNA repair mechanisms
The importance of DNA repair is evident from the large investment that cells make in:
DNA enzymes
Following the inactivation of a DNA repair gene, there is an:
Increased rate of mutaiton
DNA of each human cell loses about ______ bases everyday
5000 purine bases
Purine bases in DNA are lost daily due to the process of:
Deoxyribose hydrolyzation of N-glycosyl linkages
The spontaneous reaction of Deoxyribose hydrolyzation of N-glycosyl linkages
Depurination
A spontaneous deamination of cytosine in uracil in DNA occurs at rate of about _____ per cell per day
100 bases
DNA bases are also occasionally damaged by an encounter with:
Reactive metabolites
Ultraviolet radiation from the sun can produce a covalent linkage between two adjacent pyrimidine bases in DNA to form:
Thymine dimers
What type of linkage is produced & what bases are affected in DNA when thymine dimers are formed due to UV
Covalent linkages; pyrimidines
Hydrolytic attack includes:
Deamination & depurination
The most frequent spontaneous reactions
Hydrolytic attack
Oxidative damage to the DNA occurs due to generation of:
Reactive oxygen species
Hydrolytic attacks cleave off a base so you now have the deoxyribose base in the chain but:
No base associated with it
About 3% of the C nucleotides in vertebrate DNAs are _____ to help in controlling gene expression
Methylated
When 5-methyl cysteine nucleotides are accidentally deaminated they form the natural nucleotide:
Thymine
When the 5-methyl cytosine nucleotides are accidentally deaminated they form the natural nucleotide thymine however this T will be paired with _____ on the opposite strand, forming a _____
Guanine; mismatched base
About 1/3 of inherited human disorders are:
Single base mutations
The spontaneous deamination products of A & G are recognized as unnatural when they occur in DNA and thus are:
Readily recognized and repaired
Unnatural based are recognized and removed by a specific:
DNA glycosylase
The process of unnatural bases being removed by specific DNA glycosylase:
Base excision repair
If we have a hydrolytic attack of:
Adenine —->
Guanine —->
Cytosine —->
Thymine —->
Hypoxanthine
Xanthine
Uracil
Thymine= no deamination because there is no amino group to remove
Cytosine to uracil in DNA that is estimated to occur at a rate of 100 bases per genome per day
Deamination
The loss of 5000 A or G bases per day in each daughter cell due to thermal disruption of the N-glycosyl linkages to deoxyribose
Depurination
Thymine dimers are permutagenic lesions that alter the structure of DNA and consquently inhibit ____ & arrest _____
Polymerases
Replication
Dimers may be repaired by ____ or ____
Photoreactivation or nucleotide excision repair
Unrepaired dimers are:
Mutagenic
How do chemical modifications of nucleotides produce mutations in the case of deamination
DNA substitution (point mutation)
How do chemical modifications of nucleotides produce mutations in the case of depurinations
DNA deletions
In both DNA deamination and depurinations one strand:
Remains unchanged
Process that involves a specific nuclease that Carie’s out a regions of the strand that has the thymine dimer and then removes the damaged DNA & polymerase & ligase come in to heal it by synthesizing the short stretch that has been removed
Nucleotide excision repair
Single base pair changes often get repaired by _____ that involves a set of enzymes that are involved in removing the nick and replacing it using the other strand as a template to put back the nucleotide that was removed
Base excision repair
A location in DNA that has neither a purine nor pyrimidine base
AP site (apurinic/apyrmidinic site)
Double stranded breaks can efficiently be repaired by:
- Non-homologous end joining
- Homologous recombination
Non-homologous end joining is considered:
Quick & dirty
In the non-homologous end joining process- you have a nick in one strand and a nick in the other strand and what happens the nucleotides will be removed to create ______ so there is not extra material there & they can be rejoined
Blunt ends
When a few nucleotides get removed from the sequence through the quick & dirty repair process these are referred to as:
Scars
Homologous recombination only occurs in phases:
S & G2
When the damage of the double stranded break is repaired using information from the sister pair of the chromosomes from that gene
Homologous recombination
Both non-homologous end joining & homologous recombination result in the delay of progression from:
G1 to S phase & S to M phase
If each member of a chromosome pair contains the same allele
Homozygous
If each member of a chromosome pair carries a different allele
Heterozygous
Generally speaking _____ expresses the most sever phenotype
Homozygous dominant
But the case of ____ genes you only observe the phenotype in the homozygous recessive state
Recessive
The phenotype of a _____ gene will be observed in both the homozygous and heterozygous state
Dominant
Fancy way of saying you inherit one maternal & one paternal copy of a gene
Principle of segregation
Sexually reproducing organisms possess genes that occur in pairs and that only one ember of this pair is transmitted to the offspring
Principle of segregation
Gene at different loci are transmitted independently
Principle of independent assortment
Just because you inherit a copy of gene A doesn’t mean you are always going to inherit copy A of another gene
Principle of independent assortment
Mechanism to:
1- accurately repair double strand DNA breaks
2- exchange bits of genetic information
3- assures accurate chromosome segregation during meiosis
Homologous recombination
Homologous recombination has manny common features found in all cells & its guided by:
DNA base-pairing
In homologous recombination, inadvertent joining of two segments from different chromosomes that result in chromosomal translocations often result in:
Disease
Homologous recombination repairs double-stranded breaks:
Accurately
In the process of homologous recombination there is an exonuclease that degrades the ____ ends as DNA synthesis occurs
5’
In homologous recombination- as the exonuclease is degrading the 5’ ends as DNA synthesis occurs, there is also a migration of one strand onto the sister chromatid of the pair of chromosomes and that then becomes the:
Template
Hallmark of homologous recombination
Holliday junction
Kind of a branching point where you see one strand invading the other strand & using the other strand as a template for completing DNA synthesis
Holliday junction
Cross-strand exchange during homologous recombination
Holliday junction
The process of two DNA strands switching partner between two double helices creates a:
Holliday junction
We commonly see homologous recombination action during the _____ process
Meiosis
Sort of an alternative path that can take place depending on where cleavage takes place in the process of homologous recombination
Holliday junction
During homologous recombination- depending on where the cleavage takes place will determine whether ______ takes place or not
Crossing over
During the process of homologous recombination- cleavage location that does not result in crossing over will form a _______ while cleavage that results in the chromosomes crossing over will form a _______
Heteroduplex
Cross-over complex
Homologous recombination will take place between any two areas dependent upon:
How far apart they are
Genetic unit that defines the frequency for with which crossing over takes place as a percentage
Centimorgan
1 centimorgan =
1 cross over in 100 meiosis
1 centimorgan in DNA corresponds to about:
One million basepairs
DNA is under constant pressure to:
Acquire changes in its DNA sequence
Various types of mutations occur in DNA, some of which will give rise to ______ of any given gene
Altered protein variants
