DNA mutations

What is a DNA mutation?

A change in the DNA nucleotide sequence that can create genetic variation.

What are the two broad sources of DNA damage shown in the slides?

Exogenous (external) and endogenous (internal) sources.

What does exogenous mean?

Originating from outside the cell or organism.

What does endogenous mean?

Originating from within the cell or organism.

What does ROS stand for?

Reactive oxygen species, which can contribute to endogenous DNA damage.

What is a point mutation?

A mutation affecting a single nucleotide position in DNA.

What is DNA proofreading?

A repair process in which DNA polymerase detects and removes an incorrectly added nucleotide during DNA replication.

What enzyme activity allows DNA polymerase to proofread?

3′-to-5′ exonuclease activity, which removes an incorrectly added nucleotide.

What is mismatch repair?

A DNA repair mechanism that detects and corrects mismatched bases that remain after replication proofreading.

Which components are involved in mismatch repair according to the slides?

DNA polymerase III, repair enzymes, and DNA ligase.

What is excision repair?

A repair mechanism that removes damaged DNA and replaces the affected section.

Which components are involved in excision repair according to the slides?

DNA polymerase I, repair enzymes, and DNA ligase.

What is DNA ligase's role in repair?

It joins DNA sections by sealing breaks in the DNA backbone.

What is a thymine dimer?

An abnormal link between adjacent thymine bases in DNA, which can be caused by ultraviolet (UV) light.

What can UV-induced thymine dimers do to DNA?

They distort DNA and can interfere with normal DNA replication.

What is tautomerization?

A spontaneous shift of a DNA base into an alternative chemical form that changes its preferred base-pairing partner.

How can tautomeric shifts cause mutations?

An altered base can pair with the wrong nucleotide, potentially producing a mutation after DNA replication.

What are the normal DNA base-pairing partners?

Adenine (A) pairs with thymine (T), and guanine (G) pairs with cytosine (C).

What alternative pairings are shown for tautomeric forms in the slides?

T* pairs with G, A* pairs with C, G* pairs with T, and C* pairs with A.

What is a double-strand break?

Damage in which both strands of a DNA double helix are broken.

What can cause double-strand breaks according to the slides?

Ionizing radiation (IR).

What is non-homologous end joining (NHEJ)?

A DNA repair mechanism that joins broken DNA ends back together.

Why can NHEJ cause mutations?

It can rejoin broken DNA ends inaccurately, introducing errors into the DNA sequence.

What mutation types can result from NHEJ in the slides?

Deletion, insertion, and inversion.

What is a deletion mutation?

A mutation in which DNA sequence is lost.

What is an insertion mutation?

A mutation in which additional DNA sequence is inserted.

What is an inversion mutation?

A mutation in which a DNA segment is reversed in orientation.

What are InDel mutations?

Insertions or deletions of DNA sequence.

How can DNA polymerase slippage cause InDel mutations?

Slippage during DNA replication can cause nucleotides to be inserted or deleted from the DNA sequence.

What are transposable elements (TEs)?

Mobile DNA sequences that can move or insert copies of themselves at different genomic locations; also called jumping genes.

Who is associated with the discovery of transposable elements?

Barbara McClintock, who studied them in maize and received the Nobel Prize in 1983.

How much of the human genome contains transposable elements according to the slides?

Approximately 50%.

How many human genes contain transposable elements according to the slides?

Approximately 70–80% of human genes, with up to 1,000 transposable elements per gene.

Why are most transposable elements inactive?

Most have accumulated inactivating mutations that prevent transposition, and the host also silences many active elements.

What happens when a transposable element inserts into a non-coding region?

Its effect is generally silent, according to the slides.

What can happen when a transposable element inserts into a protein-coding gene?

It can cause a mutation that contributes to disease.

How can transposable elements contribute to gene shuffling?

Their movement or excision can rearrange gene sequences or change which promoter regulates a gene.

What disease example is associated with a transposable element in the slides?

Insertion of an L1 transposable element into the Factor VIII gene is shown as causing a hemophilia phenotype.

What are Alu elements?

A type of transposable element; the slides state that humans have over one million copies.

How can transposable elements increase genome size?

Their sequences can insert additional DNA copies throughout the genome.

What is the overall importance of DNA repair mechanisms?

They help correct DNA damage or replication errors, although some repair processes can introduce mutations.