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CYTOGENETICS
LESSON 3
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Nagh Farah A. Bang
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DNA is the genetic material of the body
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FRIEDRICH MIESCHER (1871):
Described DNA when he isolated nuclei from white blood cells in pus on soiled bandages
Discovered an acidic substance containing nitrogen and phosphorus in the nuclei, named NUCLEIN, later called NUCLEIC ACID
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ARCHIBALD GARROD
(
1902
):
Linked
inherited
disease and
protein
Noted that people with certain
inborn
errors of
metabolism
did not have certain
enzymes
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FREDERICK GRIFFITH (1928):
Identified DNA as the genetic material through experiments with Streptococcus pneumoniae bacteria
Experiment 1 (Type R Bacteria): Rough texture, mouse immune system recognizes and kills them
Experiment 2 (Type S Bacteria): Smooth texture due to capsule, mouse immune system can't recognize and kills them
Experiment 3 (Heated Type S): Control experiment, heating killed bacteria preventing pneumonia
Experiment 4 (Heated Type S + Type R): Mixture caused pneumonia due to transformation of DNA
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OSWALD
AVERY
,
COLIN MACLEOD
, MACLYN
MCCARTY
(
1944
):
Hypothesized DNA as Griffith's "transforming principle"
Treatment with
deoxyribonuclease
disrupted transformation, confirming DNA as genetic material
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ALFRED AND MARTHA CHASE (1953):
Radioactive experiments showed DNA, not protein, as the genetic material
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ERWIN CHARGAF
(
1950s
):
Showed
DNA
contains
equal
amounts of
adenine-thymine
and
guanine-cytosine
bases
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MAURICE WILKINS AND ROSALIND FRANKLIN:
Used X-ray diffraction to reveal DNA's helix structure
Franklin distinguished "A" and "B" forms of DNA
Watson and Crick discovered the double helix structure
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WATSON AND CRICK:
Discovered DNA's double helix structure using cardboard cutouts
Built the Ball and Stick Model
Received the Nobel Prize
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DNA STRUCTURE:
Gene specifies amino acid sequence in a protein
Nucleotide consists of deoxyribose sugar, phosphate group, and nitrogenous base
Purines (Adenine, Guanine) have a two-ring structure
Pyrimidines (Cytosine, Thymine) have a single-ring structure
DNA sequences measured in base pairs (Kilobase and Megabase)
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POLYNUCLEOTIDE CHAINS ARE ANTIPARALLEL:
Phosphodiester bonds hold sugar and phosphates together
Polynucleotide chains create a continuous backbone
Antiparallelism works by moving clockwise, 5' to 3' and 3' to 5'
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COMPLEMENTARY BASE PAIRING:
Specific purine-pyrimidine couples
Hydrogen bonds hold base pairs together
Two hydrogen bonds join A and T, three hydrogen bonds join G and C
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DNA CONFIGURATION IN THE NUCLEUS:
Length of stretched-out DNA of the smallest human
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DNA Configuration in the Nucleus
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Stretched out DNA of the smallest human chromosome is 14 millimeters (thousands of a meter)
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During cell division, DNA shrinks inside a nucleus by a factor of 7,000
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Proteins that compress the DNA
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Scaffold proteins form frameworks that guide DNA strands
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Histones are where DNA coils around, forming structures that resemble beads on a string
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Nucleosome is a DNA bead, a unit of chromatin structure consisting of DNA coiled around an octet of histone proteins
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Characteristics of DNA
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DNA wraps at several levels until it is compacted into a chromatid
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A nucleosome is composed of eight histone proteins (a pair of each of four types) plus the 147 nucleotides of DNA entwined around them
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A
fifth
type of histone protein anchors
nucleosomes
to short "
linker
" regions of DNA
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The
linkers
tighten the
nucleosomes
into
fibers 30 nanometers
(
nm
) in
diameter
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Only
small
sections of the DNA
double
helix are exposed
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Chromatin
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Chromatin
is
chromosome substance
,
colored materials
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It consists of 30% histone proteins, 30% scaffold proteins and other proteins that bind DNA, 30% DNA, and 10% RNA
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CTCF is an anchor protein that brings together parts of the DNA sequence within the same long DNA molecule to form the overall "loop-ome" structure
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Discovering the Structure of DNA
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Phoebus Levene identified the 5-carbon sugars ribose and deoxyribose, revealing the chemical distinction between RNA and DNA
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Erwin Chargaff analyzed the base composition of DNA from various species and observed regular relationships
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Rosalind Franklin and Maurice Wilkins used x-ray techniques
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James Watson and Francis Crick deciphered the structure of DNA, forming a double helix
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DNA Structure
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A
gene
is a section of a DNA molecule, with the order of bases specifying the
amino acid
sequence in a protein
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A nucleotide is composed of a
deoxyribose sugar
, a
phosphate group
, and a
nitrogenous base
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Purines (Guanine and Adenine) are composed of a
two-ring nitrogenous base
structure
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Pyrimidines (Cytosine and Thymine) are composed of a one-ring nitrogenous base structure
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