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