DNA Repair: damage and mutation

Question 1

Short term consequences of DNA damage

Answer 1

Reduced proliferation

altered gene expression

cell death

Question 2

Long term consequences of DNA damage

Answer 2

Aging

diseases especially cancer

Question 3

Errors of Replication

Answer 3

wrong base is incorporated by DNA polymerase

only occurs during S phase of cell division

Question 4

Spontaneous Lesions

Answer 4

Chemical changes that occur spontaneously

Exposure to mutagens: sunlight, radioactivity, ionizing radiation

occurs in resting cell

Question 5

Tautomerism

Answer 5

ability of certain chemicals to exist as a mixture of two interconvertible isomers

Question 6

Blooms syndrome

Answer 6

Defect in gene encoding DNA helicase enzyme
causes torsional strain upstream and chromosomal inability

Autosomal recessive

Question 7

Characteristics of Blooms Syndrome

Answer 7

Smaller than average

narrow chin, prominent nose and ears

Facial rash upon exposure to sun

often get diabetes and have neurological, lung and immune system deficiencies

Question 8

Depurination

Answer 8

Breaking of glycosidic bond between base and sugar in purine nucleotides

Sugar phosphate backbone remains but base is lost

Formation of apurinic sites

Question 9

Deamination

Answer 9

Loss of amine group from a base

ex)Cytosine deaminates to form uracil

Question 10

Oxidative damage

Answer 10

Result of the production of reactive oxidative compounds due to oxidative metabolism

Causes oxidative damage to many parts of the cell including addition of oxygen groups to nucleotide bases

Question 11

UV radiation

Answer 11

Generates several deleterious photoproducts
cyclobutane, pyrimidine dimers, 6-4 photoproducts

covalent linkages between adjacent pyrimidine bases on the same strand

The dimers will interfere with normal base pairing and block replication

Question 12

Nucleotide excision

Answer 12

Removes more than a few bases around a damaged site

How pyrimidine dimers formed by UV damage are repaired

Question 13

Excision repair

Answer 13

Recognition of damage

Recruit endonucleases

Region excised

DNA Polymerase fills in gap

Ligase seal nick

Question 14

Xeroderma Pigmentosa

Answer 14

Autosomal recessive

Locus heterogeneity- many genes involved in the pathway

Clinical sun sensitivity

DNA Damage is cumulative and irreversible

Question 15

what is an example of a reason why some regions would be considered a mutation hotspot?

Answer 15

deamination

ex) 5 methyl cytosine deaminating to form thymine
- creates T-G base pairing instead of C-G
- The repair machinery has to guess whether to correct the mistake back to C or leave the T base pair in DNA

Question 16

BRCA1 & 2 (autosomal dominant)

Answer 16

Process affected: repair by homologous recombination

Women with the mutation for either gene have an 85% risk of developing breast cancer by age 70

risk of developing ovarian cancer

Question 17

Ataxia Telangiectasia

Answer 17

Defects in ATM gene(11q22-23)

Autosomal recessive inheritance pattern

increased cancer risk
Affects cerebellum and immune system

Ocular telangiectasia common

Question 18

ATM gene(11q22-23)

Answer 18

Serine-threonine protein kinase responsible for detecting DNA damage and activating cell cycle arrest and DNA repair proteins(like p53)

Question 19

UV Light

Answer 19

Generation of deleterious photoproducts
-pyrimidine dimers or thymine dimers

The dimers will interfere with normal base pairing and block replication

Question 20

Hereditary nonpolyposis colon cancer

Answer 20

Autosomal dominant

resulted from mutations in genes encoding mismatch repair proteins MSH2, MLH1,PMS1, PMS2, MSH6

Results in micro satellite instability