DNA mutations and repair (10.3)

Question 1

DNA polymerase: slippage

Answer 1

During DNA replication, sometimes DNA pol “slips” when replicating repetitive regions. This can lead to an expansion of the repetitive sequence

Question 2

Trinucleotide repeat disorders

Answer 2

Huntington’s disease, Fragile-x syndrome, Freidrich’s ataxia

Question 3

Genetic anticipation

Answer 3

described the phenomenon when a genetic disorder is passed on to the next generation, the symptoms become apparent at an earlier age in each generation

Question 4

main sources of DNA damage

Answer 4

Reactive oxygen species
chemical damage
Ionizing radiation (X-rays)

Question 5

main sources of mutations

Answer 5

UV: causes distortions to DNA helix and interferes with DNA replication and gene expression

Question 6

Direct repair

Answer 6

Direct repair enzymes recognize and remove chemical modifications
Different direct repair enzymes that each recognize a different type of modification
With direct repair, the phosphate backbone of a DNA chain is not interrupted

Question 7

Mismatch repair

Answer 7

Follows DNA replication
Fixes mismatches left behind by DNA polymerase
The steps of MMR include
1.Recognizing a mismatch
2.Resecting a portion of DNA (nucleases)
3.Resynthesizing the gap (polymerases)
4.Sealing the gap (ligases)

Question 8

Base excision repair (BER)

Answer 8

fixes mismatches or chemically modifications to a base by removing and replacing 1 nucleotide
BER involves cutting and repair phosphate backbone
Glycosylases recognize specific base-pairing mistake and remove a base, leaving a hole (there are >20 different glycosylases in cells)
AP endonucleases remove sugar phosphate backbone
DNA pol adds a new nucleotide
Ligase seals the nick
BER is not always good at determining which nucleotide is the “correct” nucleotide, so sometimes the fix leads to a permanent mutation
New permanent mutations can be introduced

Question 9

What do glycosylases do in Base excision repair (BER)?

Answer 9

recognize specific base-pairing mistake and remove a base leaving a hole

Question 10

What do AP endonucleases do in Base excision repair (BER)?

Answer 10

remove sugar phosphate backbone

Question 11

Nucleotide excision repair (NER)

Answer 11

Recognize bulges and misshapen DNA structures
A segment of the DNA containing the misshapen is removed, then refilled (similar to MMR)

Question 12

Non-homologous end joining (NHEJ)

Answer 12

DS breaks can produce different type of overhangs (5’ overhangs,3’ overhangs or 5’ and 3’ overhangs)
Exonucleases and polymerases create blunt ends, by either nibbling away at the overhang or by filling in the overhang
Blunt ends are then joined by ligases to repair the break
The dsDNA break is repaired, but there are always INDELs (short insertions or deletions)
Mutagenic process

Question 13

Homologous recombination repair (HR)

Answer 13

Ds breaks are fixed by
Resecting a larger portion of the DNA (exonucleases) and finding and using the homologous chromosome as a template for new DNA synthesis
The repaired strand contains sequence identical to the homologous chromosome
Can lead to gene conversion and loss of heterozygosity

Question 14

Gene conversion

Answer 14

occurs when DNA of a heterozygous sequence is repaired using homologous recombination, resulting in the loss of heterozygosity

Question 15

Pericentric inversion

Answer 15

inversion involves the centromere, homologous chromosomes can’t align properly during meiosis, gametes will often have deletions and/or duplications

Question 16

Paracentric inversion

Answer 16

inversion doesn’t involve centromere