Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

SOM Term 1 > DNA Replication > Flashcards

DNA Replication Flashcards

1
Q

DNA REPLICATION MECHANISM

A

Semi-conservative

  • It produces two copies of the original DNA molecule, each of which contains one of original strand, and one newly synthesized strand.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Components required for synthesis of DNA

A
  • All four dNTPs (deoxynucleoside triphosphate)- bldg blocks of DNA molecule (guanosine, adenosine, thymidine, cytidine)
  • DNA template
  • DNA polymerase
  • Co-factor: Magnesium ions- required for DNA polymerase activity
  • RNA primer providing a free 3’ OH group. This primer is attached to the template SS DNA sequence
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

DNA CHAIN ELONGATION CATALYZED BY

A

DNA Polymerase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

DNA POLYMERASE

DNA synthesis in both eukaryotes and prokaryotes

A
  • Catalyzes the formation of a phosphodiester bond between the 3’ OH group of the deoxyribose in the last nucleotide to the 5’ phosphate of the dNTP precursor ( the incoming deoxynucleotide)
  • Deoxynucleoside 5’ triphosphate provides the energy source for the reaction ( cleavage of a nucleoside triphosphate to form a nucleoside monophosphate and Pyrophosphate).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Anti-viral Nucleoside analogs- viral reverse transcriptase inhibitors

A
  • AZT- Azidothymidine (Zidovudine)-deoxythymidine
  • Didanosine (ddl)—-deoxyadenosine
  • lack the 3’ OH
  • Utilized by the viral reverse transcriptase enzyme
  • Upon incorporation into the ds DNA chain, termination occurs due to the lack of 3’ OH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Anti-Viral Nucleoside analogues- Viral DNA polymerase inhibitor

A

Acyclovir——deoxyguanosine
-Only activated in infected cells. Only the infected cells possess the viral kinase

-Causes chain termination d/t lack of 3’ OH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Anti-viral Nucleotide Base analogues

A

TENOFOVIR- adenosine analog

  • competes with its natural nucleotide counterpart, deoxyadenosine 5’- triphosphate for incorporation into newly forming HIV DNA
  • Once successfully incorporated, termination of the elongating DNA chain ensues and DNA synthesis is interrupted
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Cytosine arabinose (araC)= cytosine nucleoside analogues

  • Adenosine Arabinose also acts in a similar fashion.
  • AraC has a 3’ OH group to act as an acceptor for further chain elongation. however, the OH group at position 2 prevents polymerase adding the next dNTP due to stereo restraints which results in chain termination.
A
  • Ribose sugar replaced by arabinose

* In cells it is rapidly converted to cytosine arabinose triphosphate- acts as a substrate for several human DNA pols

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

3’ to 5’ exonuclease activity

A

*DNA POLYMERASE I-as it synthesizes DNA in the 5’-3’ direction, it proofreads using the 3’-5’ exonuclease activity to remove errors. Note: Pol I uses its 5’-3’ polymerase activity to filll in gaps generated during most types of DNA repair

**only removes a nucleotide if its base is not hydrogen bonded to the template

  • BOTH DNA POLYMERASE I AND III have 3’ to 5’ exonuclease activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

5’-3’ exonuclease activity

A
  • DNA polymerase I-also removal of the primer and replacing it with DNA. Substrate must be vase paired.
  • DNA polymerase III
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Bacterial genomes

A
  • Usually circular
  • Contain single ORI
  • THETA REPLICATION at distinct sites called origins of replication (ORI)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Eukaryotic genomes/chromosomes

A
  • Many replication origins
  • No replication termini
  • LINEAR REPLICATION
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Bacteriophage (bacterial virus) and plasmids that have a DNA genome utilize

A

ROLLING CIRCLE REPLICATION

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

OriC

A

Origin of replication in E.Coli

  • Has a length of 245 no
  • contains a tandem array of three nearly identical 13-nucleotide sequences and four 9-nucleotide sequences that act as binding sites for DNA protein
  • contains DNA sequences that are A-T rich (weak bonding compared to G-C bonding). Thus the OriC facilitates easier melting and strand separation of the DNA molecule.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Initiation of DNA replication ( prokaryotes)

A
  • Initiator proteins ( DNaA protein)- binds to origins of replication and breaks hydrogen bonds between bases
  • DNA helicase(DNaB)- opens helix and binds primase to form primosome.
  • Helicase inhibitor (DNaC)-delivers helicase to DNA template
  • DNA Primase: an RNA polymerase that synthesizes the RNA primer on the lagging strand to enable DNA polymerase to syntesize DNA strand.
  • DNA polymerase I: removes the RNA primer and replace with DNA
  • DNA polymerase III: synthesis of leading and lagging strands.Synthesizes the Okazaki fragments

Note: Leading strand synthesis requires one priming event

*Single stranded DNA binding protein (ssb): binds SS DNA in the replication bubble and prevents it from annealing or forming secondary structure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Single-strand binding proteins (SSB) proteins

A

Binds to SS DNA in the replication fork to prevent reannealing and straightens out the DNA template to facilitate the DNA polymerization process.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

RNAseH and FEN-1 protein

A

Removes the RNA primer in eukaryotes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Helicase (DNaB)

A

Unwinds DNA in opposite directions away from the origin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

DNA LIGASE

A
  • Joins the Okazaki fragments together
  • LIGASE generates a phosphodiester bond between adjacent Okazaki fragments. This produces a continuous DNA strand.
  • Each Okazaki fragments requires a separate primer

-Ligase utilizes ATP as the energy source for this reaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

CLAMP PROTEIN

A

Tightly holds the DNA polymerase onto the template for synthesis of long template. There4 it increases expressively

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

DNA GYRASE ( type II topoisomerase)

A
  • Introduces negative supercoils into the DNA.
  • This reduces the positive super coils introduced by the opening of the DNA.
  • Also aids in the separation of the DNA during replication and transcription.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

CIPROFLOXACIN

A
  • A Quinolone drug that inhibits bacterial DNA gyrase ( Topoisomerase II). This results in a build up of positive supercooling ahead of the replication fork during DNA replication.
  • Used in the tx of resp and UTI infections and can also be used to treat anthrax.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q
  • Polymerase-alpha
  • synthesizes RNA primer on leading and lagging strand
  • low processitivity-falls off after synthesizing a short DNA segment
  • No exonuclease activity
  • Polymerase- sigma
  • main replicative enzyme
  • synthesizes DNA from leading and lagging strands
  • high processitivity-can syntesize long stretches of DNA.
  • 3’-5’ exonuclease proofreading activity.
A

Eukaryotic DNA polymerase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q
  • CAMPTOTHECIN
  • Anti-cancer drug
  • Binds to and inhibits topoisomerase I activity. This results in DNA damage.
  • ETOPOSIDE
  • Another anti-cancer drug
  • inhibits the activity of topoisomerase II. It prevents the re-ligation of DNA. This ultimately leads to DNA damage and apoptosis.
A

Inhibitors of Eukaryotic replication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Actinomycin D (Dactinomycin)

A

-An antibiotic derived from Streptomyces.
-Inhibitor of replication
-Planar phenoxazone ring- intercalated between adjacent guanine-cytosine bases
-polypeptide chains extend along the minor groove of the helix, thereby stabilizing the drug-DNA complex
-prevents DNA replication by: preventing the formation of regions of ssDNA.
- Binds tightly to double stranded DNA and inhibits both DNA transcription and replication.
It is effective in both prokaryotes and eukaryotes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

HOW DOES DNA POLYMERASE READ A THE TEMPLATE STRAND?

A

3’-5’ direction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

DNA PRIMASE

A
  • Addition of an RNA primer to to the template DNA
  • Synthesis of RNA primer that’s complimentary to the DNA template. The primer provides the free 3’-OH group for the synthesis of DNA.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

TELOMERES

A

A special complex containing enzymatic proteins and an RNA molecule.

  • Possesses several thousand non-coding repeated sequences- typically AGGGTT. Lengthening of DNA strand.
  • Has a protein that acts as a reverse transcriptase, as well as a short piece of RNA that can act as a template for DNA synthesis.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Polycistronic

A

PROKARYOTIC MRNA

  • MRNA that encodes several proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

In Eukaryotes the initial product of transcription must be processed, and modified to form the mature mRNA. How is it processed or modified?

A
  • 5’ cap -7-methylguanosine cap
  • Polyadenylation of the 3’ end of the mRNA
  • Splicing of Econ’s and the removal of introns
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

RNA POLYMERASE II

A

Carries a set of pre-mRNA processing proteins on its c-terminal tail

-Close up of the 5’ cap on mRNA transcripts produced

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Capping of the 5’ end performed by the following four enzymes

A
  • Phosphatase: removes a phosphate from the 5’ end of the RNA
  • THE CAPPING IS IMPORTANT BECAUSE it helps distinguish between different RNA in the cell.
  • Guanylyl transferase: adds a GMP in a reverse linkage ( 5’to 5’ instead of 5’ to 3’)
  • Guanine-7-methyl transferase: adds a methyl group to the 7 position of the terminal guanine.
  • 2’-O-methyl transferase: adds a methyl group to the 2’-O position to the next to last base on the 5th end
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

5’-methyl cap has important roles in the regulation of mRNA

A
  • Processing- prevents 5’ degradation. The CBC & elF-4E/elf-4G block the access of de-capping enzymes to then cap. This increases the half-life of the mRNA in the cytosol.
  • Transport- regulates export of mRNA out of the nucleus. mRNA is transported in complexes that contain a Cap Binding Complex (CBC) at the 5’ end and RNA binding proteins along the rest of the sequence.
  • Translation- efficient translation of the mRNA into protein. The CBC is replaced b the trajnslayion factors elF-4E and elF-4G which facilitates binding of mRNA to the ribosome.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Modification of the 3’end of the RNA is accomplished by several enzymes associated with RNA polymerase II that bind to specific sequences on the RNA.These are:

A
  • CPSF- Cleavage and Polyadenylation Specificity Factor which binds to the hexamer AAUAAA ( the Polyadenylation signal)
  • CstF- Cleavage stimulating factor F binds the G-U rich element beyond the cleavage site.
  • Cleavage factors bind to the CA sequence at the cleavage site
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

PABP

Poly-A Binding Proteins

A

-Binds to the poly-A tail and assist in directing translation by the ribosome.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Functions of 3’ mRNA polyadenylation

A
  • Increases the half-life of the mRNA by protecting it from degradation in the cytoplasm.
  • PABP binds to poly A tracts protecting mRNAs from ribonuclease attack.
  • PABP interacts with e-IF 4G and this interaction is thought too lead to the stimulation of translation of eukaryotic mRNAs
  • Aids in transcription termination
  • AIDS in the export of the mRNA from the nucleus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Econ’s

A

Protein coding sequences

38
Q

Introns

A

Non-coding sequences

39
Q

GU

A

5’ end of the intron consensus sequence

40
Q

AG

A

3’ end of the intron consensus sequence

41
Q

Small nuclear ribonucleoprotein particles (SnRNP) and numerous other splicing factors mediate splicing. These are;

A

U1
U2
U4
U5
U6
-They form base pairs with consensus sequences at each end of the intron.
-After the 5 snRNPs bind the primary transcript, U1 and U4 leave, this activating the spliceosome.
- U2,U5 and U6 interact to bring neighboring Exons into correct alignment allowing for two trans-esterification reactions to occur.

42
Q

Lariat structure

A
  • The 2nd-OH of the branch site A attacks the 5’ phosphate (p) at the splice donor site ( 5’ end of the intron) forming a 2’—-5’ unusual phosphodiester bond.
  • This reaction also leaves a free 3’ hydroxyl at the end of exon 1 which will participate in the next reaction.
43
Q

Systemic Lupus Erythematosus

A

An autoimmune disease with multiple symptoms; extreme fatigue, arthritis, fever, skin rashes, and kidney problems.

  • It is a condn in which individuals antibodies of a person react against their own nuclear proteins such as the U1 RNA component of the spliceosome, his tones, and topoisomerase.
44
Q

Alternative Splicing

A
  • Helps to increase biological diversity

- Allows a number of different proteins to be produced from the same gene

45
Q

Alpha- Tropomyosin

A

A protein with many isoforms; from regulating actin filaments in muscle cells (muscle contraction) and non- muscle cells ( cell division and shape).

46
Q

RNA EDITING

A

Chemical modification of mRNA is known as RNA editing.

  • RNA editing is a process in which information changes at the level of mRNA
  • Coding properties of transcript are altered. Information changes at the level of mRNA
  • Results in the alteration in the amino acid sequence of the specified protein and generation of functionally different proteins
47
Q

TWO DIFFERENT TYPES OF RNA EDITING

A

*Adenosine to Inosine ( A-I)
(Editing of the Glutamate receptor ) which results in a codon change within the from glutamine to arginine.
* The editing affects an amino acid located in the inner wall of the ion channel and alters calcium ion permeability.

  • This editing is a requirement for proper brain development.
  • Enzyme: Adenosine deaminase
  • Cytidine to Uridine ( C-U)
    Creates a stop codon (CAA-UAA)
  • Enzyme: Cytidine deaminase enzyme
    Ex; Apo-B gene encodes two alternative forms of the apolipoprotein B: Apo-B100 ( liver) and Apo-48 ( intestine)
48
Q

Metaphase of Mitosis

A
  • Chromosomes maximally condensed
  • karyotyping
  • Chromosomes align at equator
49
Q

Anaphase of mitosis

A

Sister chromatids separate

50
Q

Prohase I of Meiosis I

A

Homologous recombination/crossover; Oocytes arrested in prophase I- UNTIL ovulation

51
Q

Anaphase I of meiosis I

A

Homologous chromosomes randomlysegregate

52
Q

Anaphase II

A

Sister chromatids of a chromosome separate

53
Q

NON-DISJUNCTION

A

Non-separation of the homologous chromosomes/sister chromatids in the meiotic I and II respectively

  • Increased with paternal or maternal age
  • Results in a higher risk of trisomy (chromosomal abnormality) in the fetus.
  • Higher paternal age, greater the risk of development of errors during replication ( new dominant single gene mutations)
54
Q

Turner syndrome

A

45X

55
Q

Klinefelter syndrome

A

XXY

*Male with an extra X chromosome

56
Q

Maternal uniparental disobey

A

When both copies of a pair of homologous chromosomes are derived from mom

57
Q

Paternal uniparental disomy

A

When both copies of a homologous chromosome pair are derived from dad

58
Q

Types of cells

A
  • Labile cells- multiply throughout life; skin, GIT, epithelial cells. Most susceptible to cancer
  • Stable cells- G0 phase ( QUIESCENT) phase. Can divide appropriately if stimulated. Ex. Liver cells.
  • Permanent cells: Have lost ability to divide, But still able to perform their functions. Permanently in G0. Ex. neurons and cardiac muscle cells
  • Permanent cells
59
Q

P53

A

Tumor Suppressor

  • ‘Guardian of the genome’
  • DNA damage results in increased levels of p53 protein which causes;
  • Cell cycle arrest or activation of GI-S checkpoint
  • Activates DNA repair systems
  • If damage is extensive, may cause Apoptosis
60
Q

Mosaicism

A

Presence of two or more populations of cells with different genotypes in an individual

61
Q

Lariat structure

A

During intron removal from a pre-mRNA molecule;

-The 2’-OH of the branch site A attacks the 5’ phosphate (p) at the splice donor site ( 5’ end of the intron) forming a 2’ to 5’ unusual phosphodiester bond. This reaction produces a Lariat structure.

62
Q

Alternative Splicing

A

Can produce different forms of a protein from the same gene

63
Q

Beta-thalassemia

A

Many individuals with this disorder have mutations in the beta globin gene that generates additional splice sites within the mRNA

64
Q

Limb Girdle Muscular Dystrophy

A

Some pts with this disorder possess a mutation in the calpain-3 gene that generates a new splice site within exon 16

  • This results in a shorter calpain-3 mRNA that is missing many base pairs in exon 16
  • mutation interrupts a codon causing downstream codons to be out of frame and thus producing a defective protein.
65
Q

Two types of mosaicism

A
  1. The mixed somatic/Germaine mosaic; the karyotype analysis shows a mixture of cells; Normal cells ( 46XX); and cells with aneuploidy ( 47, XX+21)
  2. Confined germ line mosaic where all somatic cells are from one genotype
    - Gametes have a different genotype so there is a high risk of having children with a genetic disorder
66
Q

Meiosis

A

Takes place in the germ cell lines ( cells of the ovary or testis)

  • Gametes are haploid ( n; 23 chromosomes)
67
Q

Meiosis 1

A
  • Crossing over-genetic diversity
  • homologous chromosomes separate ( reduction division) (n; 2d)
  • 23 chromosomes and 46 sister chromatids
  • Begins with one diploid parent cell and ends with two haploid daughter cells halving the number of chromosomes in each cell.
68
Q

Meiosis II

A

Sister chromatids of chromosomes separate ( n;d)

  • starts with two haploid parent cells and ends with with four haploid daughter cells, maintaining the number of chromosomes in each cell.
  • so there are 23 chromosomes, and 23 chromatids
69
Q

FISH

A

Fluorescence in situation hybridization can be used to detect small deletions or identify chromosomes involved in complex rearrangements

70
Q

Cycling

A

A set of proteins that regulate the events of the cell cycle. They are expresses at specific points in the cell cycle. Cyclins interact with and activate cyclin-dependent kinases (Cdk proteins), enabling them to phosphorylate other proteins required to proceed through the cell cycle. The cell commits at the restriction point at which time Cyclin D accumulates and interacts with Cdks 4 and 6. this leads to phosphorylation of the Rb protein, which releases transcription factors from inhibition, in turn leading to synthesis of Cyclins A and E, which interact with Cdk2 to initiate DNA synthesis.

71
Q

Variable Number Tandem Repeat (VNTR)

A

This is a location in a genome where a short nucleotide sequence is organized as a tandem repeat. These can be found on many chromosomes, and often show variations in length ( number of repeats) among individuals.

72
Q

What are the four types of polymorphisms?

A
  1. SNP- Single Nucleotide Polymorphism; consist of a single base pair change, and may occur anywhere in a gene, including an exon, as well as between genes.SNPs are usually detected by a variety of DNA- sequencing- based techniques.
  2. Short Sequence Repeats ( SSR);stretches of DNA in which a di, tri, or tetranucleotide sequence is repeated multiple times. Vary from individual to individual. Can be measured by polymerase chain reaction (PCR) amplification, electrophoresis.
  3. Short tandem repeats or VNTR ( Variable Number Tandem Repeat); repeats of tens to hundreds of bases, with the exact number of repeats being polymorphic.
  4. Copy Number Variation or LCR- Low Copy Repeat; which consists of different numbers of copies of a specific genetic sequence.
73
Q

Xist gene

A

Involved in x-inactivation ( Lyonization)

  • this gene produces an RNA that coats the X-chromosome
74
Q

Chromosome Nomenclature

A

MSA

  • Metacentric Chromosome; p and q arms are of equal length. Centromere in the center; chromosome 1
  • Submetacentric Chromosome; p arm is shorter than q arm; chromosome 4
  • Acrocentric Chromosome; p arm contains little genetic information. Chromosome 13,14,15,21,22; involved in Robertsonian translocation.
75
Q

What are the different modes of inheritance?

A
  • Autosomal dominant and Autosomal recessive
  • X-linked dominant and X- linked recessive

*Y- linked inheritance
THE ABOVE ARE CONSIDERED MENDELIAN MODES OF INHERITANCE
* Mitochondrial inheritance- NON-MENDELIAN INHERITANCE

76
Q

Autosomal Disorders

A
  • Familial hypercholesteromia d/t LDL receptor deficiency
  • Marfan syndrome
  • Osteogenesis Imperfecta-brittle bone disease
  • Achondroplasia
  • NF-I; Neurofibromatosis type 1
  • Acute intermittent porphyria-a heme synthesis deficiency.

-Huntington disease
-Myotonic dystrophy
These are triplet repeat expansion disorders.

77
Q

Trinucleotide Repeat Disorders; Triplet Repeat Expansion Disorders

A

-Huntington’s Disease-CAG
-Myotonic Dystrophy-CTG
These are Autosomal Dominant disorders

-Fragile X - is a X-linked disorder-CGG abt 200 plus no
-Fredrich’s Ataxia-GAA
-

78
Q

PLEIOTROPIC

A

Producing or having multiple effects from a single gene

79
Q

Gangliosides

A

Glycolipids containing NANA ( N- acetyl neuraminic acid)

80
Q

Glycolipids

A

Gangliosides
Globosides
Cerebrosides

81
Q

Glycerophospholipids

A

Phosphatidylethanolamine
Phosphatidylinositol
Cardio lip in

82
Q

Sphingomyelin

A

Sphingophospholipid

83
Q

Triaglycerol

A

Storage lipid and is present in cell membrane

84
Q

Two essential fatty acids

A

Alpha- linolenic acid- Omega 3 fatty acid

Linoleic acid- Omega 6 fatty acid

85
Q

Omega 3 fatty acids

A

Alpha- Linolenic
DHA
EPA

86
Q

Omega 6 fatty acids

A

linoleic acid

ARA- Arachnidonic acid

87
Q

Saturated fatty acids

A

Palmitic acid

Stearic acid

88
Q

Lipids; fixative and stain

A

Osmium tetroxide

89
Q

Claudins and Occluding

A

Tight junctions

90
Q

Integrins

A

Hemidesomosomes

SOM Term 1 (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions