W - BIOL200 - 3.4-3.5 TELOMERASE AND TYPES OF DNA MUTATIONS

 Why can't RNA primers be added to the 3' end of lagging strand in eukaryotes?

Because there’s no room at the end for a primer to attach.

What does telomerase do?

Extends the 3' end of the lagging strand by adding DNA using an RNA template.

Why don’t prokaryotes need telomerase?

They have circular chromosomes; both forks meet in the middle.

 What does DNA polymerase do after telomerase extends the strand?

It replicates the 3′ end using the added sequence.

Why don't prokaryotic chromosomes need telomerase?

Because they are circular.

 What happens if telomerase doesn't work?

 Telomeres shorten with each division.

What is a point mutation?

 Mutation of a single base pair.

 Causes of point mutations?

Replication errors, UV, toxins, metabolic byproducts.

 3 types of point mutations?

• Silent: no AA change

• Missense: one AA changed

Nonsense: introduces stop codon

Example of nonsense mutation?

 UGC → UGA (Cys → Stop)

Example of missense mutation?

UGC → UGG (Cys → Trp)

Example of silent mutation?

UGC → UGU (Cys → Cys)

Nonsense mutation mnemonic?

STOP the NONSENSE!

What are base substitutions?

One nucleotide replaced by another.

Two types of substitutions?

• Transition: purine↔purine / pyrimidine↔pyrimidine

Transversion: purine↔pyrimidine

What causes a frameshift mutation?

Insertion or deletion that shifts the reading frame.

What happens in a deletion frameshift?

A base is lost, shifting the codon reading.

What happens in an insertion frameshift?

An extra base is added, shifting the codon reading.

What does reading frame mean?

 It’s how codons are grouped (3 bases = 1 codon).

Why is frameshift dangerous?

 It changes all downstream amino acids.

What happens with TGTGAA → TGTTGAA?

Frameshift causing premature stop (TGA).

What is DNA slippage?

Polymerase slips off and misaligns on re-binding.

 What does backward slippage cause?

 Insertion of 1 base pair.

 What does forward slippage cause?

Deletion of 1 base pair.

What is a copy number variation?

Difference in number of gene/gene region copies.

Causes of copy number variations?

• Unequal crossover in meiosis

• Non-homologous end joining

• Mobile elements

What are mobile elements?

 DNA segments that move within the genome.

Do jumping mobile elements increase copy number?

No, only copy-paste ones do.

 What are Alu elements? 

Human transposons; 11% of genome.

What is insertional mutagenesis?

When mobile elements disrupt genes by inserting.

Diseases caused by Alu elements?

Hemophilia, leukemia, muscular dystrophy.