DNA Damage and Repair Flashcards

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1
Q

What are the causes of DNA Damage?

A

Replication Errors
Chemicals
Radiation

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2
Q

Fill out the following diagram about DNA repair mechanisms

A
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3
Q

Chemical Damage
Types

A

Deamination
Depurination
Base Adducts
Base Alkylation

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4
Q

Chemical Damage
What is Deamination?

A

Transition of C/G to T/A during replication

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5
Q

Chemical Damage
Causes of Deamination

A

Nitrous Oxide
Spontaneous

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6
Q

Chemical Damage
What is Depurination?

A

Hydrolysis of the N-glycosyl linkage producing a basic site in the DNA

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7
Q

Chemical Damage
What is the effect of Depurination?

A

Deoxyribose lacking Adenine and Guanine bases

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8
Q

Chemical Damage
What is produced when tobacco is burnt?

A

Benzo[a]pyrenes or Polycyclic Aromatic Hydrocarbons

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9
Q

Chemical Damage
What is Benzopyrene converted to inside the body?

A

Epoxides

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10
Q

Chemical Damage
What effect can Epoxides have on DNA?

A

Base Adducts: Form bulky attachment onto the DNA

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11
Q

Chemical Damage
What happens when Epoxides are replicated?

A

DNA Polymerase replaces Adenine opposite Guanine instead of Cytosine

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12
Q

Chemical Damage
What effect does Nitrosamine have on DNA?

Nitrosamine is produced by tobacco

A

Base Alkylation: Alkylation of Guanine which interferes with replication

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13
Q

Physical Damage
Types

A

Ultraviolet Radiation
Ionizing Radiation

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14
Q

Physical Damage
Effect of UV Radiation

A

Cross-links adjacent pyrimidines on same DNA strand forming pyramidine dimers

Typically, a dimer forms between two Thymines

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15
Q

Physical Damage
Effect of Ionizing Radiation

A

Causes Double-Stranded Break

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16
Q

Replication Errors
Types

A

Transition: Replacement of base with base of same category (i.e. purine with purine or pyramidine with pyramidine)
Transversion: Replacement of base with base of another category (i.e. purine with pyramidine or pyramidine with purine)

17
Q

When may Insertions and Deletions occur?

A

Insertions and Deletions: Non-homologous end joining
Deletions: Replication Errors

18
Q

What happens if DNA Damage occurs?

A

Apoptosis
DNA Mutation

19
Q

What are the stages of DNA Repair?

A

Removal of Damage
Replacement of Damage

20
Q

What are the types of DNA Damage Repair?

A

Mismatch Repair
Nucleotide Excision Repair
Base Excision Repair
Double Stranded Break Repair

21
Q

Mismatch Repair
What is replication mismatch?

A

Replication Errors escaping proofreading

22
Q

Mismatch Repair
Which protein is involved in mismatch repair?

A

Mut proteins

23
Q

Mismatch Repair
What are the steps of Mut protein activity?

A

Identify strand with mismatch
Repair procedure

24
Q

Mismatch Repair
What are the steps of mismatch repair?

A

Endonuclease removes mismatched nucleotides + additional nucleotides
Pol III fills gap using ssDNA
DNA ligase joins ends

25
Q

Nucleotide Excision Repair
When is it used?

A

UV radiation forming DNA dimers

26
Q

Nucleotide Excision Repair
Procedure

A

UV specific endonuclease identifies dimer
Cleaves DNA segment containing dimer
Gap filled using DNA polymerase and ligase

27
Q

Base Excision Repair
When is Base Excision Repair used?

A

When bases are lost spontaneously
Deaminated, Alkylated or Methylated

28
Q

Base Excision Repair
Procedure

A

DNA Glycosylase cleaves nitrogenous base with damage
Endonuclease cleaves sugar and phosphate
Polymerase fills gap and ligase joins ends

29
Q

Double Stranded Break Repair
What may cause double stranded breaks?

A

Ionizing Radiation
Oxidative Free Radicals
Chemotherapeutic Drugs

30
Q

Double Stranded Break Repair
Types

A

Non-Homologous End Joining
Homologous Recombination

31
Q

Double Stranded Break Repair
What is Non-Homologous End Joining

A

Joining of two cut ends
May cause mutation

32
Q

Double Stranded Break Repair
What is Homologous Recombination?

A

Between Homologous Chromosomes
Causes no loss of DNA as sister chromosome used as template
Occurs in late S or G2 phase

33
Q

Examples of diseases caused by mutation in DNA repair genes

A

Breast and Ovarian Cancer
Hereditary Nonpolposis Colorectal Cancer/Lynch Syndrome
Xeroderma Pigmentosum

34
Q

Mutation of Repair Genes
Breast Cancer

A

Mutation of BRCA1 and 2 genes increase risk

35
Q

Mutation of Repair Genes
Lynch Syndrome

A

Mutations of Mut genes allowing accumulation of mutations
Causes tumors in colon

36
Q

Mutation of Repair Genes
Xeroderma Pigmentosum

A

Mutation affecting nucleotide excision repair pathway
Causes sensitivity to UV light