Module 7.1-7.2

In polyQ trinucleotide repeat expansion disorders, the repeat sequence is:

CAG

The removal of a purine from DNA.

Depurination

Ultraviolet light causes the formation of thymine _____ in DNA.

Dimers

The breakage of chromosomes.

Double-strand break

What enzymes participate in the base excision repair system of humans?

Glycosylase, DNA polymerase, DNA ligase, and AP endonuclease.

The two main mechanisms used to repair DNA double-strand breaks.

Homologous recombination repair and nonhomologous end-joining.

Proflavin

Intercalates into the double helix, causing deletions and insertions.

5-Bromo-uracil

Is incorporated into DNA instead of thymine, but can pair with guanine.

Alkylating agents covalently attach _____ or _____ groups to DNA bases, and thus disrupt their normal base pairing properties.

Methyl; ethyl

Type of error-prone DNA repair where double-strand breaks are corrected by trimming back the ends of the break and using small complementary sequences to reattach them. Tends to result in small deletions.

Microhomology-mediated end-joining

An agent that causes mutations.

Mutagen

What three things are necessary for the cell to enzymatically correct a thymine dimer?

Photolyase, chromophore, and light.

Nucleotide excision repair

Repair of errors that create bulky distortions of the double helix.

Type of error-prone DNA repair involving "sloppy" polymerases that are attracted to stalled replication forks where they add random nucleotides.

SOS system

DNA repair via homologous recombination typically occurs between:

Sister chromatids during G2 phase of the cell cycle.

Trinucleotide repeats can expand or contract due to:

Slipped mispairing during DNA replication.

A temporary change in DNA base structure due to movement of hydrogen atoms.

Tautomerization

What accounts for the low error rate in DNA replication?

The polymerase has a 3'-to-5' exonuclease.

Certain compounds have a structure similar to normal DNA bases and so can be incorporated into daughter strands during DNA replication. These compounds are called base _____.

Analogs

Base analogs induce mutations by:

Being incorporated instead of normal bases during DNA replication.

How would proflavin cause mutations?

By interacting between base pairs.

Nitrous acid

Deaminates cytosine and adenine, changing their pairing properties.

One type of DNA damage converts a cytosine to a uracil, which changes a G-C base pair to a T-A base pair after replication. This damage is due to loss of an amino group, or:

Deamination

The strand that is repaired in the mismatch repair system.

The nonmethylated strand

Repeated sequences of three bases that can change in number generation after generation.

Unstable trinucleotide repeats

Hydroxylamine

Adds -OH to cytosine, allowing it to pair with adenine.

Ethylmethane sulfonate

Adds an ethyl group to guanine, which then pair incorrectly.

A DNA repair system called _____ _____ repair removes damaged bases, such as uracil arising from deamination.

Base excision

Certain alleles of genes that cause disease due to the presence of unstable trinucleotide repeats act as pre-mutation alleles. Why?

Because, in general, the more repeats there are in a particular location, the higher the probability is for expansion or contraction.

What test is used to evaluate the mutagenicity of an agent?

The Ames test