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MolBio & Diagnostics > 05 DNA Damage and Repair > Flashcards

05 DNA Damage and Repair Flashcards

1
Q
  • Change in nucleotide sequence of DNA molecule
  • Occurs when a DNA gene is destroyed or altered in such a way that the genetic message carried originally by the gene is altered.
A

Mutation

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2
Q
  • Mutations are ____
  • Very few mutations ___ an organism
  • Many mutations are ____ in their effect
  • Some mutations are ___
A

RANDOM
“help”
NEUTRAL
HARMFUL

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3
Q

How is damaged DNA Mutated?

A
  • Substitution of base pairs
  • Deletion of base pairs
  • Insertion of base pairs
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4
Q
  • A material capable of altering the physical composition of a DNA gene in such a way that the genetic information is altered permanently.
A

Mutagen

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5
Q
  • Also called as point mutation

- Arises when a base pairs with an inappropriate partner during DNA replication

A

Base Substitution

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6
Q

Most common type of mutation includes:

  • _____- happens when a purine is replaced with another purine
  • _____- occurs when a purine is substituted for a pyrimidine or vice versa
A

Transition

Transversion

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7
Q

Point mutations in DNA sequence can either be:

A

Silent
Missence
Nonsense

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8
Q

 A base substitution changes the nucleotide but the triplet(trinucleotides) still codes for the same amino acid, thus it has no effect on the final protein product.

A

Silent

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9
Q

 A base substitution results in a codon that specifies a different amino acid and a polypeptide sequence that is different
 Creates a new triplet that codes for a different amino acid in the protein product
 May be conservative or nonconservative depending on the type of amino acid substitution

A

Missence

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10
Q

 A base substitution occurs in a stop codon, translation is truncated and the protein is most likely nonfunctional

A

Nonsense

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11
Q
  • The removal of one or more base pairs

- Results in frameshift

A

Deletion

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12
Q
  • Addition of one or more base pairs

- May lead to frameshifts depending on whether or not multiples of three base pairs are inserted.

A

Insertion

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13
Q
  • Called Mut Genes
  • Increase the mutation rate throughout an organism’s genome by disrupting DNA repair functions
  • Not entirely a bad thing as it can activate the repair system
A

Mutator Genes

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14
Q

Idea of Mutator Genes

- In the case of E. coli, in its DNA, despite having only 1 mutation, 10 other genes are mutated

A
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15
Q

DNA sequences prone to mutation:

A

GC-Rich Regions
Microsatellites
Centromeric Rearrangements
Telomeres and Subtelomeric Regions

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16
Q

Two mechanisms that promote mutagenesis of GC-rich regions:

 Spontaneous deamination (cancer mutational signature SBS1) of methylated cytosines
 ______ – example of mutational mechanism occurring at recombination hotspots and a major driver of base composition heterogeneity

A

GC-biased Gene Conversion

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17
Q

+____- have a germline mutation rate that is approximately ten times higher than other nucleotides and these changes are most prevalent at CpG dinucleotides

A

Cytosines

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18
Q

Hotspot for mutation and are commonly located within and upstream of genes

Regulate gene expression via methylation status

A

CpG islands

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19
Q

• Favors GC-rich alleles over AT-rich alleles and facilitates local GC-content increases

A

Meiotic Recombination

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20
Q

comprises 3% of the human genome

repetitive sequences that are prone to polymerase slippage and becomes a hotspot for mutation in both somatic and germline events

43 genes contain microsatellites in their coding sequence and acts as a mutational hotspot

A

Microsatellites

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21
Q

hotspot for rearrangements because it largely comprises satellite repeat DNAs and transposable elements (jumping genes that move from one location in the genome to another)

A

Centromeric Rearrangements

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22
Q

Shortened ____ trigger apoptosis which prevents the potential joining of chromosomal ends (chromosomal fusion)

Telomere crisis is seen in many cancers including chronic lymphocytic leukemia, breast cancer, colorectal adenomas and gliomas

______ are gene-rich sites of frequent meiotic recombination, they are highly polymorphic in copy number and in rearrangement thus it contributes significantly to intellectual disability, autism and birth defects

A

telomers

Subtelomeric Regions

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23
Q

DNA Damage can be categorized into two main classes based on its origin:

_____ (internal)- factors that originate within us
_____ (external)- factors that originate outside the organism

A

Endogenous

Exogenous

24
Q

The majority of the ______DNA damage arises from the chemically active DNA engaging in hydrolytic and oxidative reactions with water and reactive oxygen species (ROS), respectively, that are naturally present within cells.

______ DNA damage, on the other hand, occurs when environmental, physical and chemical agents damage the DNA

A

endogenous

Exogenous

25
Q

mutagenic chemicals that can be substitute for purines or pyrimidines during nucleic acid biosynthesis.

A

BASE ANALOGS

26
Q

the process in which electrophiles attack negatively charged DNA molecules and add carbon-containing groups called alkyl group.

A

Alkylating Agents

27
Q

______ cross-links adjacent pyrimidines on the same DNA strand, forming two major lesions

A

UV radiation

28
Q

can interact with the DNA molecules in a similar manner to UV rays.

A

Ionizing Radiation

29
Q
  • DNA may also suffer damage from the byproducts of normal cellular processes
  • include reactive oxygen species such as superoxide’s (O2 hydroxyl radicals (OH), and hydrogen peroxide (H2O2) that are generated during normal aerobic respiration which are considered as genotoxic. (produce more than 100 different types of chemical modifications in DNA, including loss of base and single-strand breaks.)
A

Byproducts Damage

30
Q

a repair system which reverses the damage done in DNA, usually found in Prokaryotes

A

Direct Reversal

31
Q
  • Uncertainty in sequences
  • Area where it is more likely to undergo mutation than the others
  • Hotspots are essential for medical research because it provides opportunity to understand oncogenic development
A

Mutational Hotspots

32
Q

Involves damage on a single strand only and uses a template which is usually the other strand to guide the correction of the damaged strand

A

Single Strand Repair

33
Q

It is the repair of two strands, damage on both strands is lethal to cell which causes genome rearrangement.

A

Double Strand Repair

34
Q

_____ – DNA mechanism where enzyme DNA Photolyase removes pyrimidine dimers from DNA

A

Photoreactivation

35
Q

___ – It induces formation of Pyrimidine Dimers in DNA

A

UV Radiation

36
Q

_____ – Halts DNA processes such as DNA Replication and Transcription required for the survival of cells

A

Pyrimidine Dimers

37
Q
  • Enzyme that is a product of phr Gene
  • In the ______, it binds to pyrimidine dimers
  • In the ______, binding of pyrimidine dimers fail
A

DNA Photolyase
ABSENCE OF LIGHT
PRESENCE OF LIGHT

38
Q
  • Once DNA Photolyase binds with pyrimidine dimers, PRESENCE OF LIGHT activates the enzyme and catalyzes the monomerization of pyrimidine dimers
A

Photoreactivation Mechanism

39
Q
  • Process of repairing pyrimidine dimers
  • Common for DNA lesions caused by UV radiation which distorts DNA structure
  • Carried out by UvrA, UvrB, UvrC (UvrABCcomplex) and UvrD
A

Nucleotide Excision Repair

40
Q

____Scans the DNA for presence of distortion due to pyrimidine dimers

____ identifies distortions in DNA, once it identifies dimers, it leaves the complex

A

UvrA and UvrB complex

UvrA

41
Q

_____Binds with UvrB to form UvrBC complex which plays a role in the removal of damaged DNA
_____ protein cleaves the phosphodiester bond 4 nucleotides downstream to the DNA Damage site
_____ protein cleaves the phosphodiester bond 8 nucleotides upstream to the DNA damage site

A

UvrC protein
UvrB
UvrC

42
Q
  • UvrD protein
  • Unwind the DNA and removes the DNA fragment having the size of 12 nucleotides DNA Polymerase I
  • Adds nucleotides in 5’-3’ direction
A

Helicase II

43
Q

______ – Adds nucleotides in 5’-3’ direction

A

DNA Polymerase I

44
Q

_____ – Seals the gap between the phosphodiester bond

A

DNA Ligase

45
Q

In the case of nucleotide excision repair not working properly
- A cell with DNA Damage exists
A cell undergoes through these three stages:

____ –Dormant stage where cell ages but does not divide anymore
______ – Suicide of cell
______ – Cells will divide uncontrollably causing cancer (Example: Melanoma- an accumulation of Pyrimidine Dimers that cause DNA damage)

A

Senescence
Apoptosis
Unregulated Cell Division

46
Q
  • Identifies the strand that contains methylated adenine

- Mechanism by which mismatch are removed

A

Mismatch Repair System

47
Q

Proteins Involved Repair in Mismatch:

A

Mut S
Mut L
Mut H
UVRD

48
Q
  • Protein that recognizes mismatch in nucleotides

- Also known as Mismatch Recognition Protein

A

Mut S

49
Q
  • Binds Mut S proteins
A

Mut L

50
Q
  • Binds Mut S-Mut L complex
  • Acts as Type II endonuclease
  • It searches for the nearest GATC sequence with methylated adenine, once identified, it cleaves at the daughter strand
A

Mut H

51
Q
  • Also known as Helicase II

- Unwinds the cleaved strand

A

UVRD

52
Q
  • A protein involved in crossing over during meiosis, grasps area damaged and moves it to the other section of the replication fork where the other strand has successfully replicated.
A

RecA

53
Q

Controls the SOS repair system which is activated upon DMA damage

A

SOS Operon

54
Q

– Bind to the promoter region of the SOS operon leading to the repression of all SOS responding genes (Thus, when DNA is not damaged, SOS response system is off)

A

LexA protein

55
Q

_____ – Inhibitor of LexA protein through cleaving, leaving it unable to bind to promotor site, thus there is no repression of SOS operon and the SOS response is induced

  • Activated when DNA is damaged
A

RecA protein

MolBio & Diagnostics (7 decks)

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