Diseases of Defective DNA Repair

Question 1

How do mutations occur via DNA replication?

Answer 1

Anything prevent DNA or RNA polymerases from adding the correct new nucleotides

Question 2

2 types of silent mutations

Answer 2

1) Mutation in DNA that has no function (junk DNA…no protein)
2) Mutation that does not alter the function of the sequence

Question 3

DNA Replication errors

Answer 3

Can cause mutations by adding wrong nucleotide

Question 4

Deaminating agents act on ______ and what is example

Answer 4

C,A,G

Nitrous acid (from nitrates or nitrites like bacon)

Question 5

Base analogs can

Answer 5

Be incorporated into DNA

Question 6

Alkylating agents and example

Answer 6

Add alkyl groups to base to block correct pairing

Mustard gas

Question 7

Intercalating agents and examples

Answer 7

Ethidium bromide
Benzopyrene in cigarette smoke

Slide between stacked bases and distort double helix to cause errors

Question 8

Types of radiation damage

Answer 8

DNA strand breakage (large deletions)

Dimerization of adjacent thymine bases (inhibits DNA replication)

Question 9

Deamination problem

Answer 9

Changes one base into another and pairs with wrong base

Question 10

What happens to beznopyrene in cells

Answer 10

Altered by CYP1A1 (hydroxylated)…added to DNA to create benzopyrene-DNA adduct

Question 11

3 DNA repair mechanisms

Answer 11

Direct repair
Excision repair
Mismatch repair

Question 12

Direct repair

Answer 12

Repairs thymine dimers and alkylated bases…repair proteins scan and look for lesions…once it is found, repairs without cleaving DNA or removing the base

Question 13

Excision repair

Answer 13

Repairs thymine dimers and deaminated bases

1) Proteins recognize damage and endonuclease cuts backbone on both sides
2) Exonuclease removes damaged DNA segment
3) A DNA polymerase fills in gap and ligase seals the nick

Question 14

Mismatch repair

Answer 14

Different because it is looking for regular bases that are paired incorrectly

1) As soon as rep fork passes sequence, mismatch repair enzymes scan newly synthesized DNA and replace
2) Enzymes use parental strand as template for DNA syntehsis repair

Question 15

Example of DNA repair

Answer 15

Alkyltransferase reaction removes methyl groups from DNA bases

Question 16

Example of excision repair

Answer 16

Repair of damange resulting from deamination of cytosine by uracil N-glycosylase (UNG)

Question 17

UNG mechanism

Answer 17

Recognizes U/G mispairs and hydrolyzes N-glycosydic bond of deaminated cytosine

AP site recognized by second repair enzyme that removes the deoxyribose by cleaving the sugar-phosphate backbone on both sides of lesion

Gap filled by DNA polymerase/ligase

Question 18

How does mismatch repair ID the parental strand?

Answer 18

More methylated (by Dam methylase)

Question 19

E. coli key mismatch repair proteins

Answer 19

MutS, MutL, MutH

Question 20

Difference between cytosine and 5-methylcytosine methylation

Answer 20

More efficient at turing cytosine into uracil than 5-methyl cytosine into thymidine…means amination of some can be more harmful than others

Question 21

Xeroderma pigmentosum symptoms and cause

Answer 21

Extensive freckling
Photosensitivyt
Cataracts
Frequent skin tumors

Mutation in Excision-Repair genes

Question 22

XP patients expereicne what earlier than most

Answer 22

Skin cancers

Question 23

HNPCC caused by

Answer 23

Mutations in mismatch repair proteins MLH1 and MSH2…allows for microsatellite instability

Question 24

Strand slippage is more likely in ______

Answer 24

Sequences of short nucleotide repeats

Question 25

Fanconi anemia caused by

Answer 25

Expsosure to corss-linkeing agents (chromosomes fuse)

Question 26

Fanconi anemia symptoms

Answer 26

Growht retardation and abnormal developmetn….stem cell failure…1000 fold risk of cancer

Question 27

Why is there such a big difference in penetrance/severity of symptoms?

Answer 27

Proteins work in complex (eg Fanconi Anemia complex)…each protein not equally important

Question 28

Xeroderma pigmentosum and Cockayne syndrome both involve

Answer 28

Different patients with different mutations

Question 29

Interventions for paitents with DNA repair dzs

Answer 29

Reduce exposure to mutagens

Gene therapy to deliver normal copies

Question 30

Example of gene therapy

Answer 30

Tx of SCID (severe combined immunodeficiency)