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Genetics 311 > Chapter 19: DNA Mutation & Repair (Exam 3) > Flashcards

Chapter 19: DNA Mutation & Repair (Exam 3) Flashcards

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1
Q

Depurination

A

cause of spontaneous mutation, removal of purine base from G or A

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2
Q

Deanimation

A

cause of spontaneous mutation, removal of amino group from cytosine base, DNA repair enzymes can recognize U as inappropriate and remove it, if repair system fails, C-G to A-T mutation will result in subsequent replication

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3
Q

Deamination of 5-methyl cytosine

A

cause of spontaneous mutation, thymine is normal constituent of DNA –> poses problem for repair enzymes, cannot determine which of two bases is incorrect –> hotspot for mutation

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4
Q

tautomeric shift

A

cause of spontaneous mutation, temporary change in base structure, rare, promote AC and GT bp, must occur immediately prior to DNA replication for mutation to occur

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5
Q

Mutagens

A

involved in development of human cancers, cause gene mutations that can impact future generations

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6
Q

Classifications of mutagens

A

chemical or physical

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7
Q

Chemical mutagens

A

alter DNA structure directly, base modifiers, intercalating agents

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8
Q

Base modifiers

A

covalently modify structure of a nucleotide

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9
Q

Example of base modifer

A

Nitrous Acid, replaces amino groups with keto groups

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10
Q

Intercalating Agents

A

contain flat planar structures that intercalate themselves into a double helix –> distorts helical structure –> daughter strands may have single nucleotide additions or deletions

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11
Q

Example of intercalating agent

A
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12
Q

Base analog

A

engineered to look like DNA bases but not nearly as stable, become incorporated into daughter strands during DNA replication

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13
Q

Example of base analogs

A

5-bromouracil, thymine analog, incorperated into DNA, causes incorrect base pairing, AT to GC

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14
Q

Classifications of physical mutations

A

ionizing radiation and non-ionizing radiation

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15
Q

two categories of physical mutagens

A

ionizing radiation and nonionizing radiation

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16
Q

examples of ionizing radiation

A

x-rays, gamma rays

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17
Q

properties of ionizing radiation

A

short wavelength, high energy, penetrates deeply into biological tissues (can reach gametes)
creates chemically reactive molecules: free radicals

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18
Q

what can free radicals cause

A

base deletions
single nicks in DNA strand
cross-linking
chromosomal breaks

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19
Q

examples of nonionizing radiation

A

UV light

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20
Q

properties of nonionizing radiation

A

less energy, cannot penetrate deeply
causes formation of cross-linked thymine dimers

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21
Q

thymine dimers

A

cause mutations when DNA strand is replicated
only occur at T-T sites
polymerase cannot read the TT, has to guess

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22
Q

DNA repair

A

cells contain several DNA repair systems
usually a multistep process

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23
Q

Steps of DNA repair

A
  1. irregularity in DNA detected
  2. abnormal DNA removed
  3. normal DNA synthesized (using DNA polymerase)
  4. DNA ligase seals new DNA to original strand
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24
Q

Types of DNA repair

A

direct repair
base excision repair (BER)
nucleotide excision repair (NER)
mismatch repair
homologous recombination repair
nonhomologous end joining

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25
Q

direct repair

A

not multistep
damaged bases can be directly repairs
covalent modifications of nucleotides can be reversed by specific enzymes

26
Q

two enzymes that can direct repair

A

photlyase and alkyltransferace

27
Q

photylase

A

repairs thymine dimers

28
Q

alkyltransferace

A

removal of methyl group

29
Q

base excision repair (BER)

A

uses enzymes known as DNA N-glycosylases:
can recognize abnormal base and cleaves bond between it and the sugar in DNA
A pendalases- nick backbone

30
Q

what can BER repair

A

thymine dimers, uracil

31
Q

steps of BER

A
  1. DNA N glycosylase cleaves base
  2. a penadalase nicks backbone
  3. DNA polymerase removes base
32
Q

DNA excision repair (NER)

A

repairs many types of DNA damge: thymine dimers, missing bases, chemically modified bases, some crosslinks
found in all eukaryotes and prokaryotes

33
Q

NER four key proteins (in E. coli)

A

UvrA, UvrB, UvrC, UvrD
involved in UltraViolet light Repair
recognize and remove short segment of DNA
DNA polymerase and ligase complete repair

34
Q

diseases caused by defects in NER

A

xeroderma pigmentosum (XP)
cockayne syndrome (CS)
increased sensitivity to sunlight
leads to incurable skin cancer

35
Q

mismatch repair systems

A

detect and correct a base pair mismatch
found in all organisms
specific to newly synthesized strand

36
Q

base mismatch

A

structure of DNA double helix obeys AT/GC base pairing
during replication, an incorrect base can be added
DNA polymerase have 3’ - 5’ proofreading ability which usually corrects mismatched bases

37
Q

proteins in mismatch repair (in E. coli)

A

MutL, MutH, MutS
detect mismatch and remove it from strand
can distinguish between parental and daughter strands:
prior to replication, both strands methylated
immediately after replication, parental methylated but daughter is not
cut the non-methylated (newly synthesized) strand

38
Q

double-strand breaks

A

very dangerous, breakage of chromosome into pieces
caused by ionizing radiation and chemical mutagens
occur 10-100x every day in every cell in humans
cause chromosomal rearrangements and deficiencies

39
Q

repair systems for double-strand breaks

A

homologous recombination repair (HRR)
nonhomologous end joining (NHEJ)

40
Q

homologous recombination repair (HRR)

A

results in some recombined DNA
precise repair
Steps:
1. double strand breaks
2. processes/removes 3’ ends
3. sister chromatid acts as template using strand exchange
4. DNA polymerase synthesizes DNA

41
Q

nonhomologous end joining (NHEJ)

A

not precise, lose some DNA
does not require sister chromatid nearby
1. double strand breaks
2. protein binds ends
3. proteins fill gap and synthesize new strand

42
Q

repair of activley transcribed genes

A

repaired more efficiently than non transcribed genes, easier to access
transcription makes DNA more susceptible to damage
more likely to be important for survival of organism

43
Q

mutations

A

heritable change in genetic material
provide allelic variations
foundation for evolutionary change
cause of diseases

44
Q

types of mutations

A

chromosome, genome, single gene

45
Q

point mutation

A

change in single base pair
transition: change of a pyrimidine (C. T) to another pyrimidine or a purine (A, G) to another purine
transversion: change of pyrimidine to purine / vise versa

46
Q

silent mutation

A

base substitution that does not change amino acid sequence

47
Q

missense mutation

A

base substitution that does change amino acid sequence

48
Q

nonsense muation

A

change normal codon to a stop codon

49
Q

frameshift mutation

A

addition or deletion of nucleotides in multiples of 1 or 2, change reading frame

50
Q

up promoter mutations

A

make promoter more like consenus sequence, increase rate of transcription

51
Q

down promoter mutation

A

make promoter less like consensus sequence, decrease rate of transcription

52
Q

chromosomal rearrangement

A

may break the gene itself or alter expression because of new location (position effect)

53
Q

reasons for position effects

A

movement next to regulatory sequence, movement into heterochromatic region

54
Q

germ line mutations

A

occur directly in sperm or egg cell (or a precursor)
passed through generations

55
Q

somatic mutations

A

occur in a body cell
individual with somatic mutation referred to as genetic mosaic
not passed on

56
Q

mutation rate

A

likelihood that a gene will be altered by a new mutation
expressed as number of new mutations in a given generation
range of 10^-5 - 10^-9 per generation

57
Q

things that effect mutation rates

A

larger genes have greater chance
locations that are more susceptible (hot spots)

58
Q

spontaneous mutation

A

result from abnormalities in cellular/biological processes

59
Q

induced mutations

A

caused by environmental agents

60
Q

mutagen

A

agents known to alter DNA structure

Genetics 311 (6 decks)

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