1. Chapter 3 Cells: The Living Units DNA & RNA Lecture 7, Part 2
Marieb’s Human
Anatomy and Physiology
Ninth Edition
Marieb w Hoehn
Chapter 3
Cells: The Living Units DNA & RNA
Lecture 7, Part 2
Slides 1-15; 80 min (with review of syllabus and Web sites) [Lecture 1]
Slides 16 – 38; 50 min [Lecture 2]
118 min (38 slides plus review of course Web sites and syllabus)

2. DNA Replication
The precise, accurate replication of DNA is ESSENTIAL to cellular health and viability.
DNA replication occurs during INTERPHASE of the cell cycle (in S phase).
Recall from lab – mitosis produces two identical daughter cells. This is dependent upon accurate DNA replication (recall that DNA controls all the functions and components of the cell).
Emphasize that DNA replication occurs during INTERPHASE of the cell cycle, specifically during the S phase. Strands can separate and act as templates for the synthesis of new strands.
In order for DNA replication to take place, some unwinding of DNA packing levels must take place. However, histone proteins never completely dissociate from the DNA. Somehow, DNA polymerase works around them, but more slowly than if these proteins weren’t present.
Figure from: Martini, “Human Anatomy & Physiology”, Prentice Hall, 2001

3. DNA Replication THINGS TO NOTE: Replication fork is asymmetrical5’
THINGS TO NOTE:
Replication fork is asymmetrical
New strands are synthesized in a 5’ to 3’ direction
DNA polymerase has a proofreading function (1 mistake in 109 nucleotides copied!)
Semi-conservative replication 3’ 5’ 3’ 5’ 3’ 3’ 5’
Major enzyme responsible for DNA replication is DNA polymerase. Enzyme needs a primer strand of DNA to get started. Rate is about 100 bp/sec. About 8 hours to replicate the human genome.
The one-way 5’-3’ direction of synthesis causes some unique problems. (Okazaki fragments, need for ligases)
Complementary base pairing.
Discuss semi-conservative vs. conservative replication. 3’
Figure from: Martini, “Human Anatomy & Physiology”, Prentice Hall, 2001 5’

4. RNA (Ribonucleic Acid)
RNA, like DNA, is a polynucleotide with a sugar, a phosphate, and a nitrogenous base.
However, RNA has some very important differences:
- uses the pentose sugar, ribose - uses the nitrogenous base, uracil (U) , in place of thymine (T)
- usually exists as a single-stranded molecule
Figure from: Hole’s Human A&P, 12th edition, 2010
What base do you think Uracil is capable of hydrogen bonding with?

5. mRNA Molecules Messenger RNA (mRNA) -
delivers copy of genetic information from nucleus to the cytoplasm
single polynucleotide chain
formed beside a strand of DNA
RNA nucleotides are complementary to DNA nucleotides (but remember, no thymine in RNA; replaced with uracil)
making of mRNA is transcription
If they weren’t labeled, how would we know which strand is DNA and which is RNA? (T in DNA, U in RNA)
Figure from: Hole’s Human A&P, 12th edition, 2010

6. tRNA Molecules Transfer RNA (tRNA) – the adapters in translation
carries amino acids to mRNA
carries anticodon to mRNA
translates a codon of mRNA into an amino acid
Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998

7. rRNA Molecules Ribosomal RNA (rRNA) –
provides structure and enzyme activity for ribosomes
ribosomes are necessary for protein synthesis
Where in the cell are ribosomes manufactured?
Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998

8. Mutations Mutations – change in genetic information Result when
Figure from: Hole’s Human A&P, 12th edition, 2010
Mutations – change in genetic information
Result when
extra bases are added or deleted
bases are changed
May or may not change the protein
The most common and well-known type of sickle cell disease is sickle cell anemia, also called SS disease. All types of sickle cell disease are caused by a genetic change in hemoglobin, the oxygen-carrying protein inside the red blood cells. The red blood cells of affected individuals contain a predominance of a structural variant of the usual adult hemoglobin. This variant hemoglobin, called sickle hemoglobin, has a tendency to polymerize into rod-like structures that alter the shape of the usually flexible red blood cells. The cells take on a shape that resembles the curved blade of the sickle, an agricultural tool. Sickle cells have a shorter life span than normally-shaped red blood cells. This results in chronic anemia characterized by low levels of hemoglobin and decreased numbers of red blood cells. Sickle cells are also less flexible and more sticky than normal red blood cells, and can become trapped in small blood vessels preventing blood flow. This compromises the delivery of oxygen, which can result in pain and damage to associated tissues and organs. Sickle cell disease presents with marked variability, even within families.
Repair enzymes usually correct mutations
This single point-mutation causes sickle cell disease!

9. Mutations
Recall that the 3-D structure of proteins are dependent, ultimately, upon the primary (linear) sequence of the protein.
So, a change in a single amino acid of a protein may affect the subsequent levels of protein structure.
Would such a mutation have any advantage?
What if only one allele of the -globin gene was affected?
Amino acids can be broken down into categories depending upon their side-chains. Some are hydrophobic (like Valine) and some are hydrophilic (like Glutamine). This causes a change in the 3-D structure of a protein. In the example above, a hydrophilic residue previously exposed to the aqueous environment is now turned inward away from water.

10. Chromosome-level - Karyotype
From:
Recall: Each human somatic (non-germline) cell contains two copies of each chromosome (one maternal, and one paternal). These maternal and paternal pair are homologous chromosomes. This is true except for the X and Y chromosomes, which are unpaired.
Dyes (Giemsa stain) in karyotyping distinguish between regions that are A-T rich (dark) and C-G rich (light). Produces characteristic banding pattern. The pattern of bands is unique on each chromosome.
Chromosomes 1 through 22 are numbered approximately in order of size
Female
Male
Total number of chromosomes? Number of pairs?
Number of somatic chromosomes? Number of sex chromosomes?

11. From: http://www. pathology. washington
Trisomy – error in meiosis in which one of the gametes at fertilization contributes an extra copy of a chromosome. Zygotes with extra copies of chromosomes rarely survive. Trisomy 21 is the exception (trisomy 13 and 18 rarely survive longer than a year).
Abnormal numbers of sex chromosomes – not as pronounced effects as autosomal. E.g., Klinefelter syndrome (XXY) – phenotype is male but extra X chromosome produces slightly enlarged breasts, immature testicles, and sterility.

12. Review RNA is a polynucleotide with important differences from DNA
Uses Uridine (U) rather than Thymine (T)
Uses the pentose sugar, ribose
Usually single-stranded
There are three important types of RNA
mRNA (carries code for proteins)
tRNA (the adapter for translation)
rRNA (forms ribosomes, for protein synthesis)

13. Review DNA replication During interphase
Creates an identical copy of the genetic information
Semi-conservative replication (one old, one new strand)
Uses DNA polymerase
Matches complementary bases with template
Replication forks
Error-correcting capability

14. Review Mutations are errors in the genetic material (DNA)
May affect the end-product, i.e., the protein
Vary in type and severity
Must become ‘fixed’ in the cell to be passed to future generations (sickle cell disease)
Mutations at the chromosomal level may be caused by
Deletions
Translocations
Extra copies of chromosomes