Lecture 18: DNA Mutations & Repair 🧬💥

What are transposable elements (transposons)?

Segments of DNA that can move to new locations in the genome.

What are the two main types of transposons?

LINEs (Long Interspersed Nuclear Elements) and SINEs (Short Interspersed Nuclear Elements).

What enzyme do LINEs encode and what does it do?

Reverse transcriptase, which converts LINE RNA into DNA for reinsertion.

Are transposable elements always harmful?

No, they can be harmful, neutral, or occasionally beneficial by altering gene regulation or promoting diversity.

What type of mutation arises from a replication mismatch not corrected by proofreading?

Base substitution (transition or transversion).

What is a transition mutation?

A base substitution between the same class: purine \leftrightarrow purine or pyrimidine \leftrightarrow pyrimidine.

What is a transversion mutation?

A base substitution between different classes: purine \leftrightarrow pyrimidine.

What is a tautomeric shift?

A rare chemical shift in bases that causes incorrect pairing during replication (e.g., G pairs with T).

What is replication slippage and what mutations can it cause?

Slippage during replication in repetitive regions; can cause insertions or deletions (indels).

What is depurination?

Loss of a purine base (A or G), leaving an apurinic site that usually gets an A inserted.

What mutation is commonly caused by depurination?

G \rightarrow A transition mutation.

What is deamination of cytosine?

Removal of an amine group, converting C to U.

What mutation results from unrepaired deamination of cytosine?

C \rightarrow T transition mutation.

What is oxidative DNA damage?

Damage from reactive oxygen species, commonly turning guanine into 8-oxoG.

What does 8-oxoG pair with and what mutation does it cause?

8-oxoG pairs with A, leading to a G–C \rightarrow T–A transversion.

What are base analogues and what do they do?

Fake bases that resemble real ones and mispair during replication, causing transition mutations.

What are alkylating agents?

Chemicals that add methyl/ethyl groups to DNA bases, increasing mispairing.

What are intercalating agents?

Flat molecules that wedge between DNA bases, causing indels (insertions/deletions).

What damage is caused by UV light?

Pyrimidine dimers, especially thymine dimers, that kink DNA and block replication.

What damage is caused by ionizing radiation?

Single and double-strand DNA breaks and oxidative base damage.

What is the difference between a transition and a transversion mutation?

Transition = same class base swap; transversion = purine \leftrightarrow pyrimidine.

What does excision repair do?

Recognizes and removes damaged DNA, then fills and seals the gap using polymerase and ligase.

What type of damage is repaired by base excision repair (BER)?

Small base lesions like deaminated cytosine or 8-oxoG.

What type of damage is repaired by nucleotide excision repair (NER)?

Bulky lesions like thymine dimers from UV light.

What is photorepair and what enzyme does it use?

Direct repair of thymine dimers using photolyase, activated by visible light (not present in humans).

What is homologous recombination (HR)?

Accurate repair of double-strand breaks using a sister chromatid as a template (S/G2 phase only).

What is non-homologous end joining (NHEJ)?

Error-prone repair of double-strand breaks that joins ends without a template (any cell cycle phase).

What does mismatch repair (MMR) fix?

Replication mismatches and small indels that escape DNA polymerase proofreading.

What disease is associated with defects in mismatch repair?

Lynch syndrome (hereditary nonpolyposis colorectal cancer).

What do restriction enzymes do?

Cut DNA at specific recognition sequences, producing sticky or blunt ends.

What is the recognition site for HindIII and what kind of ends does it produce?

5′-A|AGCTT-3′; it produces sticky ends with a 5′ overhang (5′-AGCTT).