Genetics Chapter 19: Gene Mutation and DNA Repair
Mutation can be:
* Changes in chromosome structure * Changes in chromosome number * Changes in DNA of a single gene
Mechanism of trinucleotide repeat
-TNREs contain at least one c and G allowing formation of a hairpin. - During replication this hairpin can lead to an increase or decrease in the length of the DNA (polymerase can slip off, hairpin forms and pulls strand back, DNA polymerase hops back on and begins synthesis from new location)
Ionizing radiation can cause....
-base deletions -oxidized bases -single nicks in the DNA strand -cross-linking -chromosomal break
Base Modifiers: Nitrous Acid
-replaces amino groups with keto groups ( NH2 to =O) - changes cytsoine to uracil and a to hypoxanthine - these don't pair with the appropriate nucleotides in the daughter strand during DNA replication
Three types of chemical mutagens
1. Base modifiers 2. intercalating agents 3. base analogues
Causes of spontaneous mutations
1. Depurination 2. Deamination 3. Tautomeric Shift
Steps of DNA repair
1. an irregularity in DNA structure is detected 2. the abnormal DNA is removed 3. normal DNA is synthesized
Two common reasons for the position effect:
1. movement to a position next to regulatory sequences 2. movement to a heterochromatic region
Test to evaluate mutagenicity (lololol fancy for talk for do it mutate? )
Ames test (WHO HATES IOWA?)
Oxidative stress may lead to...
DNA damage and mutation
Missymatchy repair system
DNA poly got 3' to 5' (3 to 5, 3 to 5 3 to 5 i always fricken forget that like idk why i can't remember that one dumb azz lil thing) proofreading ability that can detect bas mismatches and fix em (if proofreading fails the mismatch repair system saves the day)
Fix deamination
DNA repair enzymes can recognize uracil as an inappropriate base in DNA and remove it
Table 19.2
IDK if i have to know this i don't want to copy it in so go make ur lazy ass watch the video and see if he said not to memorize it, lets pray he did
Types of Physical Mutagens
Ionizing radiation, non ionizing radiation
ROS overaccumulation can lead to
Oxidative DNA damage - G is converted to 7,8-dihydro-8-oxoguanine which pairs with A during replication so GC to TA
Spontaneous mutations
Result from abnormalities in cellular/biological processes. The underlying cause originates within the cell Ex) errors in DNA replication
Point mutation
Type of gene mutation - a change in a single base pair - Can involve a base substitution (transition or transversion)
Non ionizing radiation
Uv light -less E -cannot penetrate deeply
When is a neutral missense mutation likely to occur?
When the amino acid has similar chemistry to the one it replaced
Ionizing radiation
X-rays and gamma rays -Short wavelength, high E -penetrate deeply -makes free radicals
Can gene mutation outside of the coding sequence still affect phenotype?
YEET
What happens when a repair system for deamination fails?
a C-G to A-T mutation will result during subsequent rounds of DNA replication
Position effect
a gene may be left intact, but its expression may be altered because of its new location
Tautomeric Shift
a temporary change in base structure
Other ways genes can be mutated
addition or deletion of short sequences of DNA
Mutations provide:
allelic variations
Oxidative stress
an imbalance between the production of ROS and an organism's ability to break them down.
genetic mosaic
an individual with somatic regions that are genotypically different
Missense Mutations
base substitutions in which an amino acid change does occur
Nonsense Mutations
base substitutions that change a normal codon to a stop codon
Silent Mutation
base substitutions that do not alter the amino acid sequence of the polypeptide. * Due to the degeneracy of the genetic code
Non-homologous end joining
broken ends are recognized by end binding proteins formation of crossbridge alright proteins now lets get in fromation may result in deletion of small region but it is not responsible for any lost or stolen DNA
Nucleotide Excision Repair (gold, Frankincense, and NER)
can repair lots of shit cuz its cool beans -thymine dimers and chemically modified bases -missing bases, some types of crosslinks found in all eukaryotes and prokaryotes (WILD)
Photolyase
can repair thymine dimers
Induced Mutations
caused by environmental agents, agents that are known to alter DNA structure are called mutagens (chemical or physical)
trinucleotide repeat
certain regions of the chromosome contain trinucleotide sequences repeated in tandem
Transversion
change of pyrimidine to a purine or vice versa
DNA double strand breaks can cause
chromosomal rearrangements and deficiencies
Intercalating Agents Mech
contain flat planar structures that intercalate themselves into the double helix. -this distorts the helical structure -when DNA with this is replicated, the daughter strands may contain single nucleotide additions/ deletions resulting in frameshift
down promoter mutations
decrease expression
Intercalating agents
directly interfere with replication process
non ionizing radiation can cause
formation of cross-linked thymine dimers which can cause mutations when that DNA is replicated
Riddle me this: what fixes double stranded breaks
homologous recombination repair (HRR) and nonhomologous end joining (NHEJ)
Translesion DNA polymerase
imma say it again i don't get this and i should look it up in the book but we all know I won't so good luck failing the question on this
When must tautomeric shifts occur to cause mutations?
immediately prior to replication
Base analogues
incorporate into DNA and disrupt structure. Some tautomerize at high rate
Up promoter mutations
increase expression
When do base analogues get incorporated in DNA
into the daughter strands duing replication (5-bromouracil can get incorporated instead of thymine) -tautomeric shift can result in pairing with G
Base Excision Repaire (BER--sound like the name of one of them Alaskan bush ppl u feel)
involves DNA N-glucosylases which can recognizes abnormal bases and cleave that shit between it and sugar
Frameshift mutation
involves the addition or deletion of a number of nucleotides that is not divisible by three. Results in a completely different amino acid sequence downstream of mutation.
trinucleotide repeat expansion
length of a trinucleotide repeat has increased above a certain critical size
Mutations in the core promoter can change....
levels of gene expression
Mutation Rate
likelihood that a gene will be altered by a new mutation .
What do u miiiix for an ames test? (Plz sing to the tune of what would you do for a klondike bar)
mix suspected mutagen, rat liver extract, and salmonella strain that cannot synthesize histodine. The suspected mutagen is omitted from the sample.
How is mutation rate expressed?
number of new mutations in a given gene per cell generation 10^-5 to 10^-9 per gen.
Figure 19.18
open a textbook for once and learn from that you stupid ho
What happens when replication occurs over an apurinic site?
polymerase will add a random base
Reactive Oxygen Species (ROS)
produced by aerobic organisms -hydrogen peroxide, superoxide, hydroxyl radical. Body tries to black the buildup of ROS
Consequences of tautomeric shift
promote AC and GT base pairs
Transition
pyrimidine (C, T) to another pyrimidine or a purine to a purine * These are more common than transversions
Mutation
refers to a heritable change in the genetic material
Deamination of Cytosine
removal of an amino group from the cytosine converting it into a uracil (other bases are not readily deaminated)
What that thing do? Tht thing is NER
removes damaged DNA
Chromosomal breakpoint
site of breaking and rejoining
patches of affected area are found after...
somatic mutation
Base modifiers
some covalently modify base structure, others disrupt pairing by alkylating the bases
adenine and cytosine shift:
stable amino form to imino form
Thymine and guanine shift:
stable keto form to enol form
Homologous Recomb
tbh i don't understand his slide for this so like lets j hope its not on the test
Chromosomal rearrangement may affect a gene when....
the breakpoint is within the gene
Mutation Frequency
the number of mutant genes divided by the total number of genes in a population
Depurination
the removal of a purine from the DNA forming an apurinic site. the covalent bond between deoxyribose and a purine base is somewhat unstable.
Somatic Mutations:
those that occur directly in a body cell, or in one of its precursor cells
Germ line mutation:
those that occur directly in a sperm or egg cell, or in one of their precursor cells
Germ-line mutations are passed
to half of the gametes in the next generation
Deamination of 5-methylcytosine
turns into a thymine, which is a normal constituent of DNA and so the repair system cannot determine which of the two bases on the two DNA strands is the incorrect base . HOT SPOT FOR MUTATION
Major key alter: what be the 4 key proteins of NER
uvrA,b,c, and d which recognize and remove a short segment of DNA
examples of physical mutagens
x-rays, gamma rays, UV light
Is the mutation rate constant for a given gene?
you bet ur sweet as its NOT they be varying SUBSTANTIALLY between species and even diff strains of the same species homie
describe for me plz the Ames (FACK IOWA) test
you got dis strain of bacteria (wht kind it is idk) and it cannot synthesize amino acid histidine (don't worry it happens to a lot of guys) b/c get dis shit it has a point mutation anywho a second mutation may occur restoring its ability (viagra lmao) and the ames test monitors the rate at which this mutation occurs
Can frequency be higher than rate????
yup, due to natural s and genetic drifters