U6: Molecular Basis of Inheritance Flashcards
- the two chemical components of chromosomes - _______ and ___________- emerged as the leading
candidates for the genetic material
DNA and protein
Once _______________ group showed that genes exist as parts of chromosomes, the two chemical components of chromosomes – DNA and protein- emerged as the leading candidates for the genetic material
Thomas Hunt Morgan’s
Year for Frederick Griffith experiment / study
1928
British medical officer who was trying to develop a vaccine against pneumonia
Frederick Griffith
Frederick Griffith was studying this type of bacterium; a bacterium that causes pneumonia in mammals
Streptococcus pneumoniae
Explain the experiment of Frederick Griffith
Frederick Griffith studied two strains of the bacterium Streptococcus pneumoniae. The S (smooth) strain can cause pneumonia in mice; it is pathogenic because the cells have an outer capsule that protects them from an animal’s immune system. Cells of the R (rough) strain lack a capsule and are nonpathogenic. To test for the trait of pathogenicity, Griffith injected mice with the two strains
How many strains did Griffith have in his experiment? What are these strains?
Griffith had two strains (varieties) of the bacterium, one pathogenic (disease-causing) and one nonpathogenic (harmless)
hypothesized that nucleic acid might be Griffith’s “transforming principle”
OSWALD AVERY, MACLYN MCCARTY, and COLIN MACLEOD
Give the conclusion of Griffith’s experiment
The living R bacteria had been transformed into pathogenic S bacteria by an unknown, heritable substance from the dead S cells that enabled the R cells to make capsules
they observed that treating broken open type S bacteria with protease- an enzyme that dismantles protein- did not prevent the transformation of a nonvirulent to a virulent strain, but treating such bacteria with deoxyribose-nuclease (or DNase), an enzyme dismantles DNA only, did disrupt transformation
OSWALD AVERY, MACLYN MCCARTY, and COLIN MACLEOD
What year did OSWALD AVERY, MACLYN MCCARTY, and COLIN MACLEOD confirmed that DNA is the transforming principle of the bacteria?
1944
A virus that infects bacteria; also called a phage.
Bacteriophages
Other term for bacteriophages
Phage
[True or False]
→ viruses are much simpler than cells
→ a virus is little more than DNA (or sometimes RNA) enclosed by a protective coat, which is often simply protein
Both statements are true
In _________, Alfred Hershey and Martha Chase performed experiments showing that DNA is the genetic material of a phage known as T2.
1952
In 1952, who performed experiments showing that
DNA is the genetic material of a phage
known as T2.?
Alfred Hershey and Martha Chase
Alfred Hershey and Martha Chase performed experiments showing that DNA is the genetic material of a phage known as _________. This is one of the many phages that infect Escherichia coli (E. coli).
T2
A bacterium that normally lives in the intestines of mammals and is a model organism for molecular biologists
E. coli
DNA was known to be a polymer of nucleotides, each having three components: a nitrogenous (nitrogen-containing) base, a pentose sugar called deoxyribose, and a phosphate group
CHARGAFF’S RULE
Further evidence that DNA is the genetic material came from the laboratory of biochemist _______________.
Erwin Chargaff
Erwin Chargaff reported that the base composition of DNA varies from one species to another.
Give the percentage of DNA nucleotides with base A in the following organisms:
- Sea urchin
- Human
- E. coli
Chargaff found that :
- 32.8% of sea urchin DNA nucleotides have the base A
- 30.4% of human DNA nucleotides have base A and
- 24.7% of the DNA nucleotides from the bacterium E. coli have the base A
Give Chargaff’s Rule
CHARGAFF’S RULE:
1. DNA base composition varies between species.
2. For each species, the percentages of A and T bases are roughly equal, as those of G and C bases.
suggested a triple helix structure for DNA
→ this was incorrect
LINUS PAULING
bombarded DNA with X-rays using a technique called X-ray diffraction, then deduced the overall structure of the molecule from the patterns in which the X-rays were deflected
MAURICE WILKINS AND ROSALIND FRANKLIN
How many hours did Franklin took in order to obtain photo 51 of the B form in May of 1952?
100 hours
[Scientist]
→ ____________ : provided a pivotal clue to deducing the three-dimensional structure of DNA. She distinguished two forms of DNAa dry, crystalline “A” form, and the wetter type seen in cells, the “B” form.
Rosalind Franklin
______ and _________ were certain of the sugar-phosphate backbone largely from photo 51, and turned their attention to the bases
Watson and Crick
opposing orientation of the two nucleotide chains in the DNA molecule
Antiparallelism
adenine and thymine number of H bonds
2 hydrogen bonds
[WHAT YEAR]
→ Watson and Crick surprised the scientific world with a succinct, one-page paper that reported their molecular model of the DNA: the double helix, which has since become the symbol of molecular biology
APRIL 1953
Rosalind Franklin had died of _____________ at the age of 37 in 1958 and was thus ineligible for the prize) [Nobel Prize can only be awarded to living person
ovarian cancer
[DNA REPLICATION ALTERNATIVE MODELS]
→ the two parental strands reassociate after acting as templates for new strands, thus restoring the parental double helix
CONSERVATIVE MODEL
[DNA REPLICATION ALTERNATIVE MODELS]
→ two strands of the parental molecule separate, and each functions as a template for synthesis of new, complementary strand
SEMICONSERVATIVE MODEL
(DNA REPLICATION ALTERNATIVE MODELS)
→ each strand of both daughter molecules contains a** mixture of old and newly** synthesized DNA
DISPERSIVE MODEL
After two years of preliminary work at the California Institute of Technology in the late 1950s, _________ AND _______________ devised a clever experiment that distinguished between the three DNA Replication models
Matthew Meselson and Franklin Stahl
site where replication of chromosomal DNA begins
ORIGINS OF REPLICATION
like many other bacterial chromosomes, is circular and has a single origin
Escherichia coli chromosome
short stretches of DNA having a specific sequence of nucleotides
ORIGINS OF REPLICATION
Eukaryotic chromosome
Y-shaped region where the parental strands of DNA are being unwound
REPLICATION FORK
Some of the proteins involved in the initiation of DNA replication.
Helicases
Single-strand binding proteins
Topoisomerase
Primase
are enzymes that untwist the double helix at the replication forks, separating the two parental strands and making them available as template strands.
Helicases
→ bind the unpaired DNA strands, keeping them from repairing
→ the untwisting of the double helix causes tighter twisting and strain ahead the replication fork
Single-strand binding proteins
→ is an enzyme that helps relieve this strain by breaking, swivelling, and rejoining DNA strands
TOPOISOMERASE
→ RNA chain synthesized by primase
→ generally, 5-10 nucleotides long
PRIMER
[Primer]
→ the new DNA strand will start from the _____________ end of the RNA primer
3’
→ catalyzes the synthesis of new DNA by adding nucleotides to a preexisting chain
DNA POLYMERASES
True or False
Escherichia coli: DNA polymerase III and DNA polymerase I
T
HELICASES are enzymes that untwist the double helix at the replication forks, separating the two parental strands and making them available as ____________
template strands
[True or False]
- E. coli chromosome is circular and has a single origin
True
[True or False]
Watson and Crick’s model predicts that when a double helix replicates, each of the two daughter molecules will have one old strand, from the parental molecule, and one newly made strand.
T
Watson and Crick’s model predicts that when a double helix replicates, each of the two daughter molecules will have one old strand and one newly made strand. This __________ can be distinguished from a __________ of replication, in which the two parental strands somehow come back together after the process. It was shown to be correct experimentally by __________.
Semi-conservative model; conservative model; Matthew Meselson and Franklin Stahl
Explain the model for DNA replication (Basic Concept)
(a) The parental molecule has two complementary strands of DNA. Each base is paired by hydrogen bonding with its specific partner, A with T and G with C.
(b) First, the two DNA strands are separated. Each parental strand can now serve as a template for a new, complementary strand.
c) Nucleotides complementary to the parental strand are connected to form the sugar-phosphate backbones of the new “daughter” strands.
Purine + Purine in DNA = __________
Too wide
Pyrimidine + Pyrimidine in DNA = __________
Too narrow
[TRUE OR FALSE]
- Purine + pyrimidine: width consistent with X-ray data
TRUE
Adenine can form __________ hydrogen bonds with thymine and only thymine
2
Guanine forms _________ hydrogen bonds with cytosine and only cytosine.
3
[Determine what DNA Model]
All four strands of DNA following replication have a mixture of old and new DNA
Dispersive model
What are the three alternative models? Explain each.
(a) Conservative model.
(b) Semiconservative model
(c) Dispersive model.
The two parental strands reassociate after acting as templates for new strands, thus restoring the parental double helix.
Conservative model.
Watson’s and Crick’s model of a double helix was supported by what following information? Explain.
- Rosalind Franklin concluded the sugar-phosphate backbones were on the outside of the DNA molecule and the nitrogenous bases in the molecule’s interior.
- The two sugar-phosphate backbones are anti-parallel (their subunits run in opposite directions).
- A pairs with T, and G pairs with C due to hydrogen bonds between them and a uniform diameter.
What was the additional evidence that DNA was the genetic material?
- It came from studies of viruses that infect bacteria; these viruses are called __________
Bacteriophages
Explain the synthesis of the Lagging Strand
- Primase joins RNA nucleotides into a primer.
- DNA pol III adds DNA nucleotides to the primer, forming Okazaki fragment 1.
- After reaching the next RNA primer, DNA pol III detaches.
- Fragment 2 is primed. Then, DNA pol III adds DNA nucleotides, detaching when it reaches the fragment 1 primer.
- DNA pol I replaces the RNA with DNA, adding nucleotides to the 3’ end of fragment 2 (and, earlier, of fragment 1).
- DNA ligase forms a bond between the newest DNA and the DNA of fragment 1.
- The lagging strand in this region is now complete.
These are enzymes that proofread each nucleatide against its template as soon as it is covalently bonded to the growing strand.
DNA Polymerases
[True or False]
Errors in a completed DNA molecule are high because, during DNA replication, DNA topoisomerase proofreads each nucleotide against its template as soon as it is covalently bonded to the growing strand.
False:
Errors in a completed DNA molecule are LOW because during DNA replication, DNA polymerases proofread each nucleotide against its template as soon as it is covalently bonded to the growing strand.
Little more than DNA or sometimes RNA, is enclosed by a protective coat, which is often simply protein.
Virus
[Determine what model]
The two strands of the parental molecule separate, and each functions as a template for the synthesis of a new, complementary strand.
Semiconservative model.
[Determine what model]
Each strand of both daughter molecules contains a mixture of old and newly synthesized DNA
Dispersive model.
Who conducted this experiment?
(2) cultured E. coli for several generations in a medium containing nucleotide precursors labeled with a heavy isotope of nitrogen, 15N. They then transferred the bacteria to a medium with only 14N, a lighter isotope. They took one sample after the first DNA replication and another after the second replication. They extracted DNA from the bacteria in the samples and then centrifuged each DNA sample to separate DNA of different densities
Conclusion: The result eliminated the conservative model. They therefore concluded that DNA replication is semiconservative.
Matthew Meselson and Franklin Stahl
(Scientists) concluded that DNA replication is semiconservative
Matthew Meselson
Franklin Stahl
How many DNA molecules does a human somatic cell contain?
46 DNA molecules in its nucleus
_____________ breaks, swivels, and rejoins the parental DNA ahead of the replication fork, relieving the strain caused by unwinding
Topoisomerase
synthesizes RNA primers, using the parental DNA as a template
Primase
______ unwinds and separates the parental DNA strands.
helicase
[TRUE OR FALSE]
DNA cannot initiate the synthesis of a polynucleotide; they can only add DNA nucleotides to the end of an already existing chain that is base-paired with the template strand.
true
___________ stabilize the unwound parental strands
Single-strand binding proteins
The rate of elongation is about ____________ nucleotides per second in bacteria and ___________ per second in human cells.
500; 50
What is the nucleotide that is used to make DNA?
dATP(Deoxyadenosine triphosphate)
DNA polymerases can add nucleotides only to the free ____________ of a primer or growing DNA strand, never to the ___________
3′ end; 5′ end
A new DNA strand can elongate only in the _____________ direction.
5′ —-> 3′
The new continuous complementary DNA strand synthesized along the template strand in the mandatory 5’ to 3’ direction.
Leading strand
How many primers are required for DNA pol III to synthesize the entire leading strand?
1 primer
DNA pol III must work along the other template strand in the direction away from the replication fork. The DNA strand elongating in this direction is called the ____________________.
lagging strand
The ___________ strand is synthesized discontinuously, as a series of segments
Lagging strand
The segments of the lagging strand are called ___________________.
Okazaki fragments
The segments of the lagging strand are called Okazaki fragments, after________________, the Japanese scientist who discovered them.
Reiji Okazaki
Okazaki Fragments Length
E.coli :
Eukaryotes:
The fragments are about 1,000-2,000 nucleotides long in E. coli and 100-200 nucleotides long in eukaryotes
A linking enzyme essential for DNA replication; catalyzes the covalent bonding of the 3’ end of a new DNA fragment to the 5’ end of a growing chain.
DNA ligase
catalyzes the synthesis of new DNA by adding nucleotides to a preexisting chain
DNA POLYMERASES
[Determine the DNA Polymerases]
Escherichia coli
DNA polymerase III and DNA polymerase I
[Determine the DNA Polymerases]
Eukaryotes
At least 11 different DNA polymerases
[TRUE OR FALSE]
→ The only difference between the ATP of energy metabolism and dATP, the adenine nucleotide used to make DNA, is the sugar component, which is deoxyribose in the building block of DNA but ribose in ATP.
TRUE
joins the sugar-phosphate backbones of all the Okazaki fragment into a continuous DNA strand
DNA Ligases
[TRUE OR FALSE]
Synthesis of the leading strand and synthesis of the lagging strand does not occur concurrently. They have different rates.
False;
Synthesis of the leading strand and synthesis of the lagging strand occur concurrently and at the same rate
The lagging strand is so named because its synthesis is?
The lagging strand is so named because its synthesis is delayed slightly relative to the synthesis of the leading strand.
The lagging strand is so named because its synthesis is delayed slightly relative to the synthesis of the leading strand.
TRUE
____________ forms a bond between the newest DNA and the DNA of fragment 1.
DNA ligase
__________ begins synthesis of the RNA primer for the fifth Okazaki fragment.
Primase
Removes RNA nucleotides of primer from 5’ end and replaces them with DNA nucleotides added to 3’ end of adjacent fragment
DNA pol I
synthesizes an RNA primer at 5’ end of leading strand and at 5’ end of each Okazaki fragment of lagging strand
Primase
relieves overwinding strain ahead of replication forks by breaking, swiveling, and rejoining DNA strands
Topoisomerase
Using parental DNA as a template, synthesizes new DNA strand by adding nucleotides to an RNA primer or a pre-existing DNA strand
DNA poll III
Joins Okazaki fragments of lagging strand;
on leading strand, joins 3’ end of DNA that replaces primer to rest of leading strand DNA
DNA Ligase
[Proofreading and Repairing of DNA]
→ During DNA replication, many ____________________ proofread each nucleotide against its template as soon as it is covalently bonded to the growing strand
DNA polymerases
_________________________ : enzymes remove and replace incorrectly paired nucleotides that have resulted from replication errors
Mismatched pair
[TRUE OR FALSE]
Mismatched nucleotides sometimes evade proofreading by a DNA polymerase
TRUE
The various proteins that participate in DNA replication actually form a single large complex, a “DNA replication machine.”
The DNA Replication Complex
A segment of the strand containing the damage is cut out (excised) by a DNA cutting enzyme _________________and the resulting gap is then filled in with nucleotides, using the undamaged strand as a template
NUCLEASE
Eukaryotic chromosomal DNA molecules have special nucleotide sequences called __________ at their ends.
telomeres
Telomeres become __________ during every round of replication. Thus, as expected, telomeric DNA tends to be __________ in dividing somatic cells of older individuals and in cultured cells that have divided many times.
shorter; shorter
[PROOFREADING AND REPAIRING DNA]
→ Enzymes involved in filling the gap are DNA polymerase and DNA ligase - one such DNA repair system is called ___________
NUCLEOTIDE EXCISION REPAIR
WHAT ARE INVOLVED IN THE NUCLEOTIDE EXCISION REPAIR
DNA polymerase and DNA ligase
Enzymes that are involved in filling the gap of damaged segment of the strands are:
DNA polymerase and DNA ligase
Permanent changes that are perpetuated through successive replications are called?
Mutations
Because repair of damaged DNA is so important to the survival of an organism, it is no surprise that many different DNA repair enzymes have evolved. Almost ______________ are known in E. coli, and about _________ have been identified so far in humans
100 AND 170
Explain Nucleotide excision repair of DNA damage.
- Teams of enzymes detect and repair damaged DNA, such as this thymine dimer (often caused by ultraviolet radiation), which distorts the DNA molecule.
- A nuclease enzyme cuts the damaged DNA strand at two points, and the damaged section is removed.
- Repair synthesis by a DNA polymerase fills in the missing nucleotides, using the undamaged strand as a template.
- DNA ligase seals the free end of the new DNA to the old DNA, making the strand complete
Caused by an inherited defect in a nucleotide excision repair enzyme.
Individuals with ______ are hypersensitive to sunlight; mutations in their skin cells caused by ultraviolet light are left uncorrected, often resulting in skin cancer
Xeroderma pigmentosum (XP)
Without sun protection, children who have XP can develop skin cancer by age ______.
10
A disorder that signified the importance of DNA repair enzyme.
Xeroderma pigmentosum (XP)
[TRUE OR FALSE]
Mutations can change the phenotype of an organism. And if they occur in germ cells, which give rise to gametes, mutations can be passed on from generation to generation
True
For linear DNA, such as the DNA of eukaryotic chromosomes, the usual replication machinery cannot complete the __________________ of daughter DNA strands.
5′ ends of daughter DNA strands.
Note: This is another consequence of the fact that a DNA polymerase can add nucleotides only to the 3′ end of a preexisting polynucleotide
True or False: Most prokaryotes have a circular chromosome, with no ends, so the shortening of DNA does not occur.
True
Eukaryotic chromosomal DNA molecules have special nucleotide sequences called _____________ at their ends
Telomeres
In each human telomere, for example, the six-nucleotide sequence ____________ is repeated between ___________ and __________ times.
TTAGGG
100
1000 times
G rich tail
TTAGGG (Telomeres)
GIVE PROTECTIVE FUNCTION OF TELOMERES
- Specific proteins associated with telomeric DNA prevent the staggered ends of the daughter molecule from activating the cell’s systems for monitoring DNA damage.
- Telomeric DNA acts as a kind of buffer zone that provides some protection against the organism’s gene shortening, somewhat like how the plastic-wrapped ends of a shoelace slow down its unravelling
Specific proteins associated with ________ prevent the staggered ends of the daughter molecule from activating the cell’s systems for monitoring DNA damage.
telomeric DNA
sequences consist of short tandem repeats that contribute to the stability and integrity of chromosomes
Telomeric DNA
sequences consist of short tandem repeats that contribute to the stability and integrity of chromosomes
Telomeric DNA
acts as a kind of buffer zone that provides some protection against the organism’s gene shortening
telomeric DNA
[True or False]
Telomeres does not prevent the erosion of genes near the ends of chromosomes; they merely postpone it.
TRUE
Telomeres become ______ during every round of replication
shorter
Telomeric DNA tends to be _____________ in dividing somatic cells of older individuals and in cultured cells that have divided many times
shorter
Conditions wherein telomeres become shorter:
→ Telomeres become shorter during every round of replication
→ Telomeric DNA tends to be shorter in dividing somatic cells of older individuals and
→ Telomeric DNA in cultured cells that have divided many times
discovered an enzyme called telomerase that catalyzes the lengthening of telomeres in eukaryotic germ cells
ELIZABETH BLACKBURN and JACK SZOSTAK
ELIZABETH BLACKBURN and JACK SZOSTAK
→ discovered an enzyme called _______________ that catalyzes the lengthening of telomeres in eukaryotic germ cells
Telomerase
[TRUE OR FALSE]
→ Telomerase is NOT active in most human somatic cells, but its activity varies from tissue to tissue.
→ The activity of germ cells results in telomeres of minimum length in zygote.
First statement is true; second is false
→ Telomerase is not active in most human somatic cells, but its activity varies from tissue to tissue.
→ The activity of germ cells results in telomeres of maximum length in zygote
[True or False]
Normal shortening of telomeres may protect organisms from cancer by limiting the number of divisions that somatic cells can undergo.
TRUE
Telomerase activity is abnormally ___________ in cancerous somatic cells, suggesting that its ability to stabilize telomere length may allow these cancer cells to persist.
high
In E. coli, the chromosomal DNA consists of about 4.6 million nucleotide pairs, representing about ______________ genes.
4,400 genes
In E. coli, the chromosomal DNA consists of about ___________ nucleotide pairs, representing about 4,400 genes.
4.6 million
Proteins called _________ are responsible for the first level of DNA packing in chromatin.
histones
More than a fifth of a histone’s amino acids are ___________ charged (____ or ______) and therefore bind tightly to the negatively charged DNA.
positively charged ; (lysine or arginine)
[NUCLEOSOME]
The “string” between beads is called
Linker DNA
A nucleosome consists of DNA wound ____________ around a protein core of eight histones.
twice
This dense region of DNA in a bacterium, called the ______________, is not bounded by membrane
nucleoid
Each eukaryotic chromosome contains a single linear DNA double helix that, in humans, averages about ____________ nucleotide pairs.
1.5 * 10^8 nucleotide pairs
complex of DNA and protein, called ___________
chromatin
_____________ is a process by which nucleases cut out and other enzymes replace damaged stretches of DNA.
Nucleotide Excision Repair (NER)
The Meselson-Stahl experiment showed that DNA replication is _________________________
: The parental molecule unwinds, and each strand then serves as a template for the synthesis of a new strand according to base-pairing rules
semiconservative
