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3 - Molecular and medical genetics > 3.1 - principles of medical genetics > Flashcards

3.1 - principles of medical genetics Flashcards

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Biology 101 flashcards USMLE® Step 1 flashcards
1
Q

define gene

A

inherited units of information specifying phenotype at a gross level (morphological characteristics) or at a molecular level (particular products - proteins / RNAs)

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2
Q

mutations - types of mutation and their consequences // harmless variants vs disease-causing mutations

how do mutations occur

A

3.7

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3
Q

What is the structure of chromosomes during metaphase?

A

X shaped = centromere holds the two sister chromatids together, with telomeres at the apical regions.

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4
Q

What is a chromatid?

A

Each arm of a chromosome is referred to as a chromatid, with two chromatids forming a single chromosome during metaphase.

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5
Q

when does the chromosome exist in its familiar x shape

A

only in metaphase

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6
Q

short arm and long arm in chromosomes

A

p = short
q = long

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7
Q

What are the three types of chromosomes based on the length ratio of p (short arm) to q (long arm)?

A

Acrocentric Chromosome: Features a very short p arm (e.g., chromosome Y).

Submetacentric Chromosome: Has a shorter p arm compared to q, resulting in unequal arm lengths (e.g., chromosome 5).

Metacentric Chromosome: Displays nearly equal lengths of p and q arms (e.g., chromosome 1).

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8
Q

How do chromosomes exist during interphase?

A

In interphase, chromosomes are less condensed, appearing as a tangled mass of chromatin referred to as “a ball of spaghetti.”

Despite this disorderly appearance, specific regions are associated with particular chromosomes, indicating a structured organization.

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9
Q

How are chromosomes spatially organized within the nucleus?

A

Chromosomes are organized into specific territories within the nucleus, with distinct regions of the nucleolus associated with particular chromosome sets.

This spatial organization facilitates gene regulation and expression.

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10
Q

What is a karyotype?

A

A karyotype is a complete set of chromosomes in an organism

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11
Q

What does the human karyotype consist of?

A

The human karyotype contains 46 chromosomes in total, including 22 pairs of autosomes and 1 pair of sex chromosomes (XX in females and XY in males).

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12
Q

What are the primary functions of chromosomes?

A

Store and organize genetic information.

Ensure accurate replication and distribution of genetic material during cell division.

Regulate gene expression and facilitate cellular processes.

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13
Q

What is the role of telomeres and centromeres in chromosome function?

A

Telomeres: Repetitive DNA sequences at the ends of chromosomes that protect them from degradation and prevent fusion with neighboring chromosomes.

Centromeres: Regions of DNA that link sister chromatids and are essential for proper chromosome alignment and segregation during mitosis and meiosis.

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14
Q

DNA and RNA structure

A

deoxyribose or ribose
phosphate group
nitrogenous base

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15
Q

Why does DNA use deoxyribose instead of ribose?

A

ribose = OH on C2 instead of H

DNA uses deoxyribose because it is more stable than ribose. The extra -OH group on ribose’s 2’ carbon can act as a nucleophile, potentially leading to degradation of the RNA polymer.

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16
Q

Charge on the P-sugar backbone

A

negative

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17
Q

What are purines?

A

adenine (A) + guanine (G)

double-ring structure

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18
Q

What are pyrimidines?

A

cytosine (C), thymine (T), and uracil (U).

single ringed structure

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19
Q

What is a nucleoside?

A

nucleoside is a molecular structure formed by a nitrogenous base (either purine or pyrimidine) attached to a sugar molecule (deoxyribose in DNA or ribose in RNA).

Nucleosides do not contain a phosphate group

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20
Q

What is a nucleotide?

A

consists of a nucleoside (nitrogenous base + sugar) bonded to one or more phosphate groups.

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21
Q

How do you name nucleosides for RNA and DNA?

A

RNA Nucleosides:
Adenosine: Adenine + Ribose
Guanosine: Guanine + Ribose
Cytidine: Cytosine + Ribose
Uridine: Uracil + Ribose

DNA Nucleosides:
Deoxyadenosine: Adenine + Deoxyribose
Deoxyguanosine: Guanine + Deoxyribose
Deoxycytidine: Cytosine + Deoxyribose
Deoxythymidine: Thymine + Deoxyribose

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22
Q

How do you name RNA nucleotides, and what are some examples?

A

Adenosine Triphosphate (ATP): Adenine + Ribose + 3 Phosphates

Guanosine Triphosphate (GTP): Guanine + Ribose + 3 Phosphates

Cytidine Triphosphate (CTP): Cytosine + Ribose + 3 Phosphates

Uridine Triphosphate (UTP): Uracil + Ribose + 3 Phosphates

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23
Q

How do you name DNA nucleotides, and what are some examples?

A

Deoxyadenosine Triphosphate (dATP): Adenine + Deoxyribose + 3 Phosphates

Deoxyguanosine Triphosphate (dGTP): Guanine + Deoxyribose + 3 Phosphates

Deoxycytidine Triphosphate (dCTP): Cytosine + Deoxyribose + 3 Phosphates

Deoxythymidine Triphosphate (dTTP): Thymine + Deoxyribose + 3 Phosphates

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24
Q

What is a phosphodiester bond, and where is it found?

A

linkage between two nucleotides in a DNA or RNA strand, connecting the 3’ hydroxyl (OH) group of one sugar to the 5’ phosphate group of the next nucleotide.

forms the sugar-phosphate backbone of nucleic acids.

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25
Q

How does nucleophilic attack contribute to phosphodiester bond formation?

A

3’ hydroxyl group of the growing nucleotide chain performs a nucleophilic attack on the α-phosphate of the incoming nucleoside triphosphate

This attack facilitates the formation of the phosphodiester bond by releasing pyrophosphate (PPi).

results in cleaving of the beta and gamma phosphate and leaves a phosphodiester bond

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26
Q

What is pyrophosphate

A

two phosphate groups linked together by a high-energy bond = released from phosphodiester bond its whats left over

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27
Q

directionality of phosphodiester bond

A

3’ hydroxyl group of one nucleotide to the 5’ phosphate group of another.

creates the directionality in DNA and RNA strands, where synthesis proceeds in a 5’ to 3’ direction.

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28
Q

Oligonucleotide

A

A short chain of nucleotides (usually less than 20–25 bases).

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29
Q

DNA has directionality, meaning the two ends are distinct

A

5’ End: Typically contains a phosphate group attached to the 5’ carbon of the sugar.

3’ End: Contains a free hydroxyl (-OH) group on the 3’ carbon of the sugar.

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30
Q

what direction does DNA grow

A

DNA synthesis always occurs in the 5’-3’ direction, meaning new nucleotides are added to the 3’ end.

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31
Q

How does the DNA chain grow during replication?

A

nucleotides are added to the 3’ end, which contains the free hydroxyl group.

DNA polymerase facilitates the nucleophilic attack of the 3’-OH group on the 5’-phosphate group of the incoming nucleotide, forming a 3’-5’ phosphodiester bond.

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32
Q

What does it mean that DNA is antiparallel?

A

In the double helix, the two strands of DNA run in opposite directions:

One strand runs 5’ to 3’.
The other strand runs 3’ to 5’

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33
Q

What are the major and minor grooves in DNA?

A

major groove is the wider space between the sugar-phosphate backbones, allowing protein binding.

minor groove is the narrower space, providing less access for protein interactions.

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34
Q

What is the function of the major and minor grooves in DNA?

A

major groove facilitates binding of regulatory proteins and transcription factors, while the minor groove allows for smaller molecules to bind, influencing DNA function.

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35
Q

What is the hierarchical structure of DNA organization from nucleosomes to chromosome territories?

A

Nucleosomes: DNA wrapped around histones.

Chromatin: Compacted nucleosomes.

Chromatin Loops: Interactions between distant nucleosomes.

Topologically Associated Domains (TADs): Groups of interacting chromatin loops.

Compartments: Functionally related gene groups.

Chromosome Territories: Non-overlapping regions for individual chromosomes during cell division.

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36
Q

What is a Nucleosome?

A

A nucleosome is the fundamental unit of DNA packaging in eukaryotic cells.

basic unit of chromatin

made up of 8 histone proteins on which 146 nucleotides are wound up twice

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37
Q

what is chromatin

A

Chromatin is a complex of DNA and proteins (histones) that forms chromosomes within the nucleus.

A higher-order structure formed by the folding and compacting of nucleosomes.

Includes both euchromatin and heterochromatin

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38
Q

What is the semi-conservative model of DNA replication?

A

Each daughter DNA molecule consists of:

One original (template) strand.
One newly synthesized strand.

Ensures genetic information is preserved.

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39
Q

What did the Meselson-Stahl experiment demonstrate?

A

Proved the semi-conservative model of DNA replication.
Used E. coli grown in 15𝑁 medium to track nitrogen isotopes in DNA.

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40
Q

What methodology was used in the Meselson-Stahl experiment?

A

Step 1: E. coli bacteria were grown in a medium containing only 15 N (heavy nitrogen) for many generations.

Resulted in DNA composed entirely of nitrogen-15.

Step 2: Transferred a portion of this culture to a medium with
14𝑁 (light nitrogen) and allowed replication.

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41
Q

What were the steps taken to analyze DNA after the E. coli replication in the Meselson-Stahl experiment?

A

samples were taken at intervals after transfer to the 14 N medium.

DNA was isolated and subjected to ultracentrifugation to separate it based on density.

Analyzed bands of DNA to track incorporation of 14 N over generations:

After one generation, DNA was intermediate in density (hybrid).

After subsequent generations, increasing amounts of DNA showed only 14 𝑁 confirming the semi-conservative model.

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42
Q

directionality of DNA

A

Directionality is 5’ phosphate to 3’ OH

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43
Q

How did Rosalind Franklin contribute to the discovery of DNA’s structure?

A

used X-ray crystallography to reveal that DNA had a double-helical structure.

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44
Q

What key structural features make the DNA double helix energetically stable?

A

Hydrophilic phosphate groups face outward, while hydrophobic nitrogenous bases point inward, reducing energy and enhancing stability.

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45
Q

What primary event characterizes the S phase in the cell cycle?

A

DNA replication, where the entire genome is duplicated, occurs in the S phase (synthesis phase) of interphase

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46
Q

What is the role of helicase enzymes in DNA replication?

A

Helicase enzymes unwind the DNA double helix, separating it into two single strands to allow each strand to serve as a template for new DNA synthesis.

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47
Q

What is the role of DNA polymerases in DNA replication?

A

DNA polymerases catalyze the formation of phosphodiester bonds, linking nucleotides to form the sugar-phosphate backbone of the new DNA strand.

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48
Q

What are dNTPs, and how are they used during DNA synthesis?

A

Deoxyribonucleoside triphosphates (dNTPs) are the building blocks of DNA. DNA polymerases use dNTPs to add complementary nucleotides to the growing daughter strand.

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49
Q

Why is DNA replication described as ‘semi-conservative’?

A

In semi-conservative replication, each new DNA molecule consists of one original (parental) strand and one newly synthesized strand, conserving half of the original molecule.

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50
Q

steps in DNA replication

A
  • initation
  • elongation
  • termination
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51
Q

DNA is double stranded; where and how is it opened?

A

Origins of replications
DNA helicases

52
Q

What prevents the 2 strands from re-annealing

A

Single stranded specific binding protein: SSB (specifically RPA)

53
Q

DNA Pol cannot synthesise a chain of nucleotides form de novo- only extend from an existing short chain, which is:

A

Primase: RNA primer

54
Q

What enzymes replicate the DNA?

A

DNA polymerase
PCNA

55
Q

Polymerases can only polymerise nucleotides in a 5’ -3’ direction. How can both strands be replicated at the same time in both directions?

A

DNA polymerase on leading and lagging strand
Okazaki fragments

56
Q

How are the ends (telomeres) on the lagging strand replicated?

A

Telomerase

57
Q

Movement of the replication forks creates tension in DNA. How is this overcome?

A

Topoisomerase

58
Q

Where does DNA synthesis initiate, and what is the first step?

A

DNA synthesis initiates at Origins of Replication (ORIs), where initiator proteins bind to recruit additional proteins, forming a replication complex (replisome) around the DNA.

59
Q

What role do initiator proteins play in DNA replication?

A

Initiator proteins target ORIs, recruit other proteins to the site, and help form the replication complex, setting up the machinery for DNA synthesis.

60
Q

What is a replication fork, and how is it formed?

A

Replication forks are points where the DNA helix is opened for replication, formed at each ORI when DNA helicase unwinds the double helix.

61
Q

What is the function of DNA helicase within the replication complex?

A

DNA helicase unwinds the DNA double helix, exposing each strand as a template and hydrolyzing ATP to break hydrogen bonds between strands.

62
Q

What role does DNA primase play in the replication process?

A

DNA primase synthesizes a short RNA primer that provides a 3’ end, where DNA polymerase can begin synthesizing the new DNA strand.

63
Q

How does the requirement for an RNA primer improve replication accuracy?

A

Using an RNA primer allows for initial, temporary nucleotides, increasing accuracy and reducing errors in the DNA sequence.

64
Q

What is the complete cascade of steps in DNA initation?

A

ORIs (Origins of Replication): Sites rich in AT pairs, allowing easier strand separation.

Initiator Proteins: Bind to ORIs, causing local DNA unwinding; e.g., ORC in eukaryotes.

Formation of Pre-Replication Complex: Initiator proteins recruit helicase-loading proteins like Cdc6 and Cdt1.

Helicase Loading: Helicase is loaded onto DNA by loading factors; ATP hydrolysis activates helicase.

DNA Unwinding by Helicase: Helicase unwinds DNA, separating strands and forming replication forks.

Stabilization of Single Strands: Single-strand binding proteins (e.g., RPA) bind to protect DNA from re-annealing and nuclease activity.

Primer Synthesis: DNA primase synthesizes a short RNA primer complementary to the template.

Primer Provides 3’ OH Group: RNA primer offers a 3’ OH group, essential for DNA polymerase activity.

DNA Polymerase Binding: DNA polymerase binds to the 3’ OH end of the primer to start DNA synthesis.

Formation of the Replisome: Assembly of the full replication machinery (replisome) to drive bidirectional replication.

65
Q

In which direction can DNA polymerase extend the RNA primer?

A

DNA polymerase can only add nucleotides to the 3’ end of the template strand, requiring a free OH group.

66
Q

What is the directional limitation of DNA and RNA polymerases?

A

Both DNA and RNA polymerases synthesize new chains only in the 5’ to 3’ direction.

67
Q

How is the leading strand oriented during synthesis?

A

The leading strand is read in the 3’ to 5’ direction, allowing the new strand to be synthesized in the 5’ to 3’ direction.

68
Q

What characterizes the lagging strand during DNA replication?

A

The lagging strand is synthesized in short fragments (Okazaki fragments) due to its 5’ to 3’ directionality opposing the movement of the helicase.

69
Q

How does primase function on the lagging strand?

A

Primase moves in a 3’ to 5’ direction, depositing multiple RNA primers as the helix unwinds.

70
Q

What mechanism allows synthesis of the lagging strand?

A

The backstitch mechanism enables DNA polymerase to synthesize in short bursts, creating fragments.

71
Q

What are Okazaki fragments, and how are they formed?

A

Okazaki fragments are short DNA segments synthesized on the lagging strand, formed as RNA primers are added to newly exposed bases.

72
Q

How are Okazaki fragments linked after synthesis?

A

After synthesis, Okazaki fragments are joined together by DNA ligase to form a continuous DNA strand.

73
Q

What is the complete cascade of steps in DNA elongation during replication?

A

DNA elongation begins after DNA polymerase has attached to the RNA primer on the template strand.

DNA polymerase synthesizes new DNA in the 5’ to 3’ direction, adding nucleotides to the 3’ end of the growing strand. (deoxynucleoside triphosphates)

The template strand for the leading strand is read in the 3’ to 5’ direction, allowing continuous synthesis of the new strand.

On the leading strand, DNA polymerase synthesizes a continuous strand as the DNA helix unwinds, maintaining the same direction as the replication fork.

On the lagging strand, elongation occurs in short fragments (Okazaki fragments) because it is synthesized in the 5’ to 3’ direction, opposite to the direction of helicase movement.

Each Okazaki fragment requires a separate RNA primer synthesized by primase, providing the necessary 3’ OH group for DNA polymerase.

DNA polymerase synthesizes each Okazaki fragment in a backstitch mechanism, moving back to the primer after each fragment is completed.

DNA polymerase synthesizes Okazaki fragments by adding nucleotides to the 3’ end of each primer, resulting in discontinuous DNA synthesis on the lagging strand.

After all Okazaki fragments are synthesized, the RNA primers are removed and replaced with DNA, and DNA ligase seals the nicks between adjacent fragments to create a continuous strand.

Proofreading Function: DNA polymerase has a proofreading ability, checking for errors during elongation. It can remove incorrectly paired nucleotides using its 3’ to 5’ exonuclease activity, enhancing the fidelity of DNA replication.

74
Q

What is the primary event signaling the end of DNA replication?

A

DNA synthesis continues until the replication forks meet or until there is no more template DNA left to replicate.

75
Q

What role does RNase play in the termination phase?

A

RNase removes RNA primers at the beginning of each Okazaki fragment on the lagging strand.

76
Q

What enzyme is responsible for joining Okazaki fragments?

A

DNA ligase

77
Q

How does DNA polymerase fill gaps left by RNA primers?

A

DNA polymerase uses adjacent DNA strands as templates to fill in the gaps left by RNA primers by synthesizing new DNA nucleotides.

78
Q

What type of bond does DNA ligase form between Okazaki fragments?

A

DNA ligase catalyzes the formation of phosphodiester bonds between adjacent DNA fragments.

79
Q

What is the mechanism by which DNA ligase seals the nicks between fragments?

A

DNA ligase facilitates the nucleophilic attack of the 3’ OH group on the 5’ phosphate of the adjacent fragment, creating a covalent bond.

80
Q

What checks are performed after DNA synthesis is complete?

A

Post-replication, proofreading and repair mechanisms ensure the newly synthesized DNA is free of errors.

81
Q

How does telomerase contribute to the termination process at chromosome ends?

A

Telomerase may extend telomeres at chromosome ends to prevent the loss of essential DNA sequences during replication.

82
Q

What is the complete cascade of steps in the termination phase of DNA replication?

A

Completion of DNA Synthesis: DNA replication continues until replication forks meet or the entire template has been copied.

Random Fork Meeting: Replication forks meet randomly along the chromosome, marking the end of DNA synthesis.

Removal of RNA Primers: RNase H and other exonucleases remove RNA primers at the beginning of each Okazaki fragment on the lagging strand.

Gap Filling by DNA Polymerase: DNA polymerase uses adjacent DNA as templates to fill gaps left by removed RNA primers, replacing them with DNA nucleotides.

Joining of Okazaki Fragments: DNA ligase catalyzes the joining of Okazaki fragments by forming phosphodiester bonds between adjacent fragments.

Catalysis of Phosphodiester Bond Formation: DNA ligase facilitates the nucleophilic attack of the 3’ hydroxyl group on the 5’ phosphate of the neighboring fragment, sealing the nicks.

Completion of Continuous DNA Strand: The joining of Okazaki fragments creates a continuous DNA strand, completing the replication process.

Post-Replication Checks: After synthesis, proofreading mechanisms—primarily performed by DNA polymerase—ensure high fidelity by correcting any misincorporated nucleotides.

Telomere Replication: At the chromosome ends, telomerase may extend telomeres to prevent the loss of vital genetic information during replication.

Significance of Telomeres: Telomeres protect chromosome ends from degradation and maintain genomic stability.

Quality Control Mechanisms: Additional repair pathways (such as mismatch repair) act post-replication to correct errors and maintain genomic integrity.

83
Q

What are telomeres?

A

Telomeres are repetitive nucleotide sequences at the ends of chromosomes that protect them from degradation and prevent end-to-end fusion during cell division.

84
Q

What happens during leading strand replication regarding telomeres?

A

On the leading strand, the last nucleotide is added to the exposed 3’ OH group, allowing for complete replication of the telomere region.

85
Q

What challenges arise during lagging strand replication of telomeres?

A

The lagging strand’s replication relies on RNA primers, and the removal of the final RNA primer at the end leaves no free 3’ OH for DNA polymerase to use.

Continued shortening of the telomeres with every round of replication

86
Q

How does telomerase address telomere shortening?

A

Telomerase is a reverse transcriptase enzyme with an RNA component that uses an RNA template to synthesize a complementary DNA strand, adding telomere sequences back to the 3’ end.

87
Q

telomeres arent usually expressed in somatic cells>

A

Through every round of cell division, telomeric repeat sequences are lost -> after many divisions it results in gradual erosion of the telomere

If telomere is shortened beyond a particular point, it triggers a cascade of events -> puts cells into a senescent state so they can’t divide anymore.

88
Q

telomerase in cancer

A

Telomerase also plays a role in regulation of cell proliferation -> coordinates transition of proliferating cells into cellular senescence state where cells no longer proliferate

Cancer cells can activate the telomerase and keep it active

Telomerase is expressed ->

allows cancer cells to replicate infinitely without reaching replicative senescence ->

continually restore the length of the telomeres

89
Q

where are telomeres usually found

A

Present in cancer cells, stem cells, germline cells -> which replicate a lot

90
Q

What proofreading ability do DNA polymerases possess?

A

DNA polymerases have a proofreading ability that requires 3’–5’ exonuclease activity, enabling them to correct mistakes during DNA replication.

91
Q

How does 3’–5’ exonuclease activity work in DNA polymerases?

A

If an incorrect nucleotide is inserted during DNA synthesis, the polymerase shifts from polymerase activity to exonuclease activity to remove the erroneous nucleotide.

92
Q

What mechanism allows exonuclease to identify which nucleotide to remove?

A

The old DNA strand is typically methylated, while the newly synthesized strand remains unmethylated. The exonuclease detects the unmethylated nucleotide and removes it.

93
Q

: What happens to histones during DNA replication?

A

: Histones are removed as replication forks move forward, allowing access to the DNA template.

94
Q

: How is chromatin re-formed in daughter strands after replication?

A

One half of the histones in the daughter strands is recycled from the parental histones, while the other half consists of newly synthesized histones.

95
Q

What is the role of aminoacyl-tRNA synthetase (AARS)?

A

AARSs are enzymes that catalyze the aminoacylation reaction, covalently linking an amino acid to its corresponding tRNA.

also known as tRNA ligase

96
Q

What is a substitution mutation, and what effect can it have?

A

A substitution mutation is a point mutation where one nucleotide base is replaced by another.

It can alter a single amino acid in a protein, as in the Glu-to-Val substitution in the HBB gene that causes sickle-cell disease.

97
Q

What are the three types of substitution mutations?

A

silent mutations (no change in amino acid sequence),

nonsense mutations (introduces a stop codon, shortening the protein)

missense mutations (alters a single amino acid).

98
Q

What happens in a silent mutation, and why does it often have no effect?

A

In a silent mutation, a base change does not alter the amino acid due to redundancy in the genetic code.

usually has no effect on protein function.

99
Q

How does a nonsense mutation impact protein structure and function?

A

A nonsense mutation introduces a premature stop codon, resulting in a truncated, often nonfunctional protein

100
Q

What is a deletion mutation, and what effect does it have if it isn’t a multiple of three?

A

A deletion mutation removes nucleotide bases. If the number is not a multiple of three, it causes a frameshift, altering downstream codons and often leading to a nonfunctional protein, as seen in Duchenne muscular dystrophy.

101
Q

What are spontaneous mutations, and how do they commonly arise?

A

Occur naturally due to DNA’s chemical instability or errors during cell processes.

Nucleotide Deamination:
Cytosine deaminates to uracil, leading to base-pair mismatches.

Nucleotide Depurination:
Loss of adenine or guanine, creating abasic sites and replication errors.

Replication Errors:
DNA polymerase may misincorporate bases; if uncorrected, leads to mutations.

102
Q

How does nucleotide deamination lead to mutations, and what bases are commonly affected?

A

Changes the amino groups of bases, leading to incorrect base-pairing.

Cytosine to Uracil:
Deamination converts cytosine to uracil, pairing with adenine, causing a transition mutation.

Adenine to Hypoxanthine:
Deamination of adenine forms hypoxanthine, pairing with cytosine and causing mispairing.

103
Q

What is depurination, and why does it lead to spontaneous mutations?

A

Loss of a purine base (adenine or guanine) from DNA.

Mechanism:
Breakage of the glycosidic bond, creating an abasic site.
Mutation Potential:

DNA polymerase may insert a random base opposite the missing purine, leading to mutations.

104
Q

. How do replication errors contribute to spontaneous mutations?

A

Proofreading Limitations:
Some mismatches evade correction, leading to permanent mutations.

Strand Slippage:
DNA polymerase may slip in repetitive sequences, causing insertions or deletions, especially in microsatellites.

105
Q

What are induced mutations, and how are they different from spontaneous mutations?

A

Caused by external factors (radiation, chemicals), unlike spontaneous mutations.
Radiation:

UV light can cause thymine dimerization, disrupting DNA replication.

Chemical Agents:
Chemicals like alkylating agents add groups to nucleotides, causing mispairing or breaking strands.

106
Q

What is thymine dimerization, and how does it lead to mutations?

A

UV radiation causes adjacent thymine bases on the same DNA strand to bond, forming a cyclobutane pyrimidine dimer.

Covalent bonds form between two thymines, distorting the DNA helix structure.

Impact on DNA Replication:
Thymine dimers prevent proper base-pairing during replication.

DNA polymerase may stall or bypass the dimer, leading to errors or mutations.

Can lead to frameshift mutations or incorporation of incorrect bases.

Accumulation of thymine dimers without repair is linked to skin cancers, as seen in conditions like xeroderma pigmentosum

107
Q

What are the main types of DNA damage, and which repair mechanisms are specific to each?

A

Nucleotide Damage: Caused by chemical modifications or UV-induced dimerization; repaired by nucleotide excision repair (NER).

Single-Strand Breaks (SSBs): Usually fixed by single-strand break repair, involving ligases and enzymes specific for single-strand DNA.

Double-Strand Breaks (DSBs): Repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ).

Mismatch Damage: Errors in base-pairing, addressed by mismatch repair (MMR).

108
Q

How does nucleotide excision repair (NER) function, and what types of damage does it fix?

A

Targeted Damage: Repairs bulky lesions like thymine dimers and chemically modified bases.

A damaged nucleotide is recognized, and enzymes cut out a short DNA segment around the lesion.

DNA polymerase fills in the gap with the correct bases, and DNA ligase seals the strand.

109
Q

What is the mechanism of single-strand break repair (SSB repair), and why is it essential?

A

Fixes single-strand breaks caused by oxidative stress or DNA replication errors.

The enzyme poly (ADP-ribose) polymerase (PARP) detects the break.

SSB repair proteins stabilize the strand, DNA polymerase fills the gap, and ligase seals it.

110
Q

What is homologous recombination (HR) repair, and when is it used?

A

A repair mechanism for double-strand breaks (DSBs) using a sister chromatid as a template.

111
Q

What is non-homologous end-joining (NHEJ) repair, and when is it used?

A

A repair mechanism for double-strand breaks (DSBs) that joins DNA ends without a template.

112
Q

How does mismatch repair (MMR) correct replication errors?

A

Fixes base-pair mismatches that escape DNA polymerase proofreading.

Mismatch repair proteins (like MutS and MutL in bacteria) recognize the mismatched base.

The incorrect section is excised, and DNA polymerase fills the gap with the correct bases.

Ligase seals the repaired segment.

113
Q

consequences of mutations for protein production

A
  • loss of function
  • gain of function
114
Q

What are dominant mutations?

A

Mutations where one copy of the altered gene is sufficient to express a trait.

The transcription of one mutated gene produces a ‘toxic’ protein that has an effect

115
Q

What are recessive mutations?

A

Mutations that require both copies of the gene to be altered for the trait to be expressed.

The normal allele is sufficient to produce enough functional protein to mask the mutation (we can upregulate that gene). the mutated allele either just isnt transcribed or is non functional. (the normal allele is functional enough)

116
Q

why is a DNA polymerase with 100% fidelity selected against

A
  • not 100% fidelity is good because it introduces variation
  • but also bad because causes disease
117
Q

mutations can be spontaneous. such as slippage. what is slippage

A

A process during DNA replication where the DNA polymerase misaligns the newly synthesized strand with the template strand, leading to the addition or deletion of nucleotides.

118
Q

What is polyploidy?

A

The presence of more than two complete sets of chromosomes.

119
Q

causes and result of polyploidy

A

Dispermy: Fertilization of an egg by two sperm.

Fertilization of a diploid egg.

Can lead to a triploid embryo (3 sets of chromosomes).

Approximately 1-3% of recognized pregnancies involve triploidy; many do not survive to term.

120
Q

What is constitutional tetraploidy?

A

A rare condition where there are four complete sets of chromosomes.

Often arises from failure to complete the first zygotic division, resulting in a 4C DNA content without subsequent cytokinesis.

121
Q

What is aneuploidy?

A

Characterized by the duplication or loss of one or more individual chromosomes.

Trisomy: Three copies of a particular chromosome (e.g., Down syndrome).

Monosomy: One chromosome is absent (e.g., Turner syndrome)

122
Q

causes of aneuploidy

A

Often stems from nondisjunction during cell division (meiosis I, meiosis II, or mitosis).

123
Q

What are translocations?

A

A genetic change in which a piece of one chromosome breaks off and attaches to another chromosome, occurring between non-homologous chromosomes.

124
Q

What are reciprocal translocations?

A

The exchange of segments from two different chromosomes without a net loss of genetic information.

125
Q

What is an example of a reciprocal translocation?

A

The Philadelphia chromosome arises from a reciprocal translocation between chromosomes 9 and 22, fusing the BCR and ABL genes.

126
Q

What are non-reciprocal translocations?

A

Involve the transfer of a chromosomal segment to a different chromosome without reciprocal exchange.

127
Q

What is Robertsonian translocation?

A

A type of non-reciprocal translocation that commonly occurs between acrocentric chromosomes.

The long arms of two acrocentric chromosomes fuse at their centromeres, resulting in a single chromosome, while the short arms are typically lost.

3 - Molecular and medical genetics (1 decks)

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