Chapter 15: Mutation and Repair

What are the four types of point mutations?

• Base substitutions

• Base insertion

• Base deletion

• Indel mutation

What is base substitutions?

The substitution of different nucleotides at a specific location

What is base insertion?

The insertion of one or more nucleotide sequence at a specific location

What is base deletion?

The deletion of one or more nucleotide sequences at a specific location

What is synonymous mutation?

A mutation that changes a nucleotide but codes for the same amino acid

What is missense mutation?

A mutation that changes the identity of an amino acid residue within a protein and can be divided into 2 categories

• Conservative mutation

• Nonconservative mutation

What is conservative mutation?

A mutation that substitutes an amino acid with another that has similar biochemical properties

What is nonconservative mutation?

A mutation that replaces an amino acid with another that has different biochemical properties

What is Nonsense mutation?

A mutation that replaces an amino acid with a nonsense (aka a stop codon)

What is a frameshift mutation?

A mutation that occurs when one more nucleotide is inserted or deleted from a DNA sequence, shifting the reading frame of the gene

How does a mutated Ras gene cause cancer and tumors?

It changes a glycine into another amino acid, causing protein activity to be changed and be constantly expressed

What regulates Ras proteins?

They are regulated by GDP binding

How does GDP regulate Ras proteins?

By binding to the protein and inactivating it, and can be replaced by GTP to activate the protein

What occurs if the Ras protein is mutated?

It will prevent the protein from being able to hydrolyze GTP into GDP and become inactive, causing the protein to always be in its active state

What if the enhancer region it mutated?

It can disrupt the binding of TF to the region

What if the promoter region is mutated?

It can disrupt the binding of the RNA polymerase/GTF to the region, causing the gene to be silenced or hyper active

What is 3’ UTR frequently involved in?

In the binding of miRNA and siRNA in order to form base pairing with a target mRNA

What does 5’ UTR contain?

it contains important ribosome-binding sites that if mutated, can effect translation efficiency

What if there are mutated introns on an mRNA transcript?

It can disrupt the proper splice sites and prevent introns from being removed, leading to a huge frameshift and shortening of a protein

When can mutations occur?

They can occur in any cell at any time and at random

What is spontaneous mutation?

A type of mutation that can occur naturally from errors produced from DNA replication

What can tautomeric base pairing lead to?

It can lead to a DNA bases chemical structure to be changed

What can ionized base pairing lead to?

It can lead to base mispairing

What is replication slippage?

A mutation that occurs when a DNA polymerase detaches from a template strand during replication and reattaches to an incorrect position, causing the addition or deletion of repeated DNA sequences

What is the trinucleotide repeat disorder?

It is a genetic condition that occurs when there’s an abnormal expansion of trinucleotides (aka 3 nucleotides) within a gene due to replication slippage, causing gene function to be disrupted

What is oxidative damage?

A mutation that changes a bases identity through oxidation, resulting in DNA replication and transcription being blocked due to the changed identity

What is an alkylating agent?

A mutagen that can mutate DNA and alter the DNAs helix structure and base pairing properties

What is bulky adducts?

A mutagen that can disrupt a DNA structure within a cell, resulting in DNA replication and transcription being blocked

What are base anologs?

A mutagen that resembles a normal DNA base that can be incorporated into DNA replication, leading to a change in a single nucleotide base pair in the DNA sequence

What are intercalating agents?

they are mutagens that can cause either single or double stranded breakage, resulting in various mutations

How can you determine whether a mutagen can change DNA?

By using the Ames test that helps identify mutagens

How is the Ames test performed?

A mutated His- (salmonella typhimurium) bacteria is used to detect whether a chemical can cause mutations in DNA

What is Base exision repair?

a type of repair that removes mismatched base pairs and replaces it with the correct base

What kind of damage can base excision repair repair?

Non-bulky damage such as:

• Alkylation

• Oxidation

• Deamination

• Depurination

How does Base excision repair perform its job?

Base excision repair will remove the problematic base and use a undamaged strand as a template to place the proper base

What is nucleotide excision repair?

A type of repair that removes a DNA sequence and replaces it with the correct DNA sequence

Nucleotide excision repair is able to repair…

Pyrimidine dimers and Bulky adducts

Mismatch repair and translesion synthesis are able to repair…

Base mismatches and loops

What is translesion synthesis?

A process that helps bacteria overcome any DNA replication blockages

How does translesion synthesis help overcome DNA replication blockages?

When a DNA lesion is present, a TLS polymerase will replace the DNA polymerase and synthesize past the blockage, then DNA polymerase will take over again and continue synthesis

What is direct repair?

A repair that uses specific enzymes to either:

• remove a methyl group from a base and resynthesize DNA

• or separate covalently linked thymine from one another

When does Base, nucleotide, and direct repair occur?

During the G1 phase

When does translesion synthesis, mismatch repair, and homologous recombination occur?

During the S phase and G2 phase

What are the two potential scenarios that can occur after homologous recombination?

• No crossover occurring between two strands

• A crossover occurring between two strands

What can occur if DNA is inaccurately repaired?

It can lead to a fixed mutation in the genome that can cause consequences that are either

• beneficial

• harmful

• Neutral