Lecture 49

Question 1

what are the short-term consequences of DNA damage?

Answer 1

1. reduced proliferation
2. altered gene expression
3. apoptosis

Question 2

what are the long term consequences of DNA damage?

Answer 2

1. aging

2. disease

Question 3

What are the two classes of spontaneous mutation?

Answer 3

1. errors of replication

2. spontaneous lesions- chemical changes

Question 4

what kind of errors can occur during replication?

Answer 4

wrong base is incorporated by DNA poly

due to tautomerism sometimes thymine can be in its enol form and bind with guanine

Question 5

what is bloom syndrome?

Answer 5

A defect in the DNA helicase enzyme

characteristics:

1. smaller than average
2. narrow chin, prominent nose and ears
3. facial rash
4. chromosome instability (higher risk of cancer)

Question 6

What are the three main types of spontaneous dna damage?

Answer 6

1. depurination
2. deamination
3. oxidative damage

Question 7

explain depurination?

Answer 7

most common

breaking of glycosidic bond between base and sugar in purine nucleotides; a purine is lost

An apurinic site is the result

Question 8

explain deamination?

Answer 8

loss of an amine group from a base

cytosine will deaminate to uracil

but… 5-methyl cytosine deaminates to thymine; which will lead to bigger issues. (mutational hotspot)

Question 9

explain oxidative damage?

Answer 9

a result of the production of reactive oxidative compounds due to oxidative metabolism

can lead to a transverse mutation

Question 10

what can UV light lead to the creation of?

Answer 10

covalent linkages between adjacent pyrimdine bases on the same DNA strand.

these dimers interfere with normal base pairing and block replication

Question 11

types of repair mechanisms?

Answer 11

1. nucleotide excision
2. base excision
3. mismatch repair

Question 12

How does excision repair occur?

Answer 12

1. recognize damage
2. recruit endonucleases
3. region excised
4. DNA poly fills gap
5. ligase seals

Question 13

xeroderma pigmentosum

Answer 13

autosomal recessive disorder

mutations in NER genes

Question 14

base pair excision?

Answer 14

1. missplaced base
2. base removed by glycosylase
3. sugar phosphate removed by endonuclease
4. replace base and ligate

Question 15

mismatch repair?

Answer 15

1) Mismatch missed by proofreading is recognized by MSH proteins
2) Repair may occur during S-phase (if missed by proof-reading) or in G2 when genome is scanned for errors
3) Excision of bases around mismatch
4) Repair by re-synthesis

Question 16

how can double strand breaks be fixed?

Answer 16

1. non-homologous end joining

2. recombinational repair

Question 17

what is the result of DNA repair gene mutation?

Answer 17

1. increased error rate

2. genomic stability

Question 18

ataxia telangiectasia?

Answer 18

mutation of the ATM gene
autosomal recessive
increased cancer risk (avoid X-rays)