Download Appendix C

K.Muma
Bio 6
Appendix C
DNA Replication & Mitosis
Study Objectives:
Appendix C: DNA replication and Mitosis
1. Describe the structure of DNA and where it is found.
2. Explain complimentary base pairing: A-T and C-G
3. Describe the steps involved in DNA replication. Include the enzymes involved and
their functions.
4. Compare the replication of the leading strand vs. the lagging strand.
5. Explain why DNA replicates and when during the cell cycle it happens.
6. Describe the structure and function of a eukaryote chromosome.
What is a chromosome? How many do you have?
What are homologous chromosomes?
7. Explain why cells undergo mitosis.
8. Briefly describe the events that occur in each phase of interphase: G1, S, G2
9. Briefly describe the events that occur in each phase of mitosis: prophase, metaphase,
anaphase, telophase. What is the final result of mitosis? Which types of cells
undergo mitosis?
10. Define cytokinesis.
11. Compare and contrast the characteristics of normal cells vs. cancer cells
12. Describe factors that control cell division and the role they play in the development of
cancer: proto-oncogenes, tumor suppressor genes, apoptosis (cell death),
telomeres
Outline
DNA Replication
I.
Review of DNA Structure
a. Double stranded
i. The chemical side groups of the nitrogen bases form hydrogen
bonds, connecting the two strands.
1. Adenine forms two hydrogen bonds with thymine
2. Guanine forms three hydrogen bonds with cytosine
ii. Sugar-Phosphate Backbones run antiparallel to each other
1. Each DNA strand has a 3’ end with a free hydroxyl
group and a 5’ end with a free phosphate group (See figure
14- 6 in textbook)
2. One strand runs 5’ to 3’ and the other runs 3’ to 5’
3. Sketch two DNA strands running antiparallel to each other
and label the 5’ and 3’ ends.
II.
DNA Replication
a. Purpose - before a cell divides it must replicate its DNA so each daughter
cell has a full set of DNA
b. Mechanism: Semiconservative – the two parent strands serve as a template
for the synthesis of the new complementary strands (See figure 14.7 and
14.8)
c. Steps in replication:
i. Replication Origin - begins at special sites called origins of
replication
1. There may be hundreds or thousands of origin sites per
chromosome.
2. Strands separate forming a replication “bubble” with
replication forks at each end.
3. The replication bubbles elongate as the DNA is replicated
and eventually fuses with other replication bubbles
4. Enzymes Involved
a. Helicase – unwinds and unzips the DNA helix at the
replication forks
b. Topoisomerases – relieves the torque from the
unwinding DNA
ii. Elongation of new strand
1. Primase – constructs RNA primer complementary to the
DNA templates
2. After formation of the primer, DNA polymerase III –
elongates the new strand by adding nucleotides to the 3’end
(~50 per second)
3. Replication always occurs in the 5’ to 3’ direction
a. Leading strand – elongates toward the replication
fork, continuous
b. Lagging strand – elongates away from the
replication fork
i. Results in Okazaki fragments:
discontinuous short segments
c. Sketch your original template strands and then add
your leading and lagging strands. Label your 5’
and 3’ ends on your template strands so you can
determine your leading and lagging strand:
4. DNA polymerase I – replaces RNA primers with DNA
nucleotides
5. Ligase – enzyme that joins fragments into a single DNA
strand
III.
Proofreading and Repair
a. Replication is extremely accurate
i. 1 error per billion nucleotides
b. DNA polymerase proofreads each nucleotide against the template and
fixes any mismatches
c. Causes of mistakes
i. replication errors
ii. physical and chemical agents
**Note: DNA replication only occurs when the cell is preparing to divide. When the cell
is NOT dividing DNA is used as a blueprint for protein synthesis.
Outline
Cell Division – Mitosis
I.
Why do cells divide?
a. To grow
b. To repair damaged cells
c. To replace lost cells
d. To reproduce
II.
Chromosomes in Eukaryotes -long threads of DNA wrap around proteins
called histones
a. Chromatin -when a cell is not dividing the DNA is loose & unwound
b. Chromosomes - when the cell divides the chromatin condenses into
tightly
c. Chromosome number – humans have 46 chromosomes (23 pairs)
i. “n” is the number of different types of chromosomes
1. in humans n =23
ii. Humans are diploid (2n) therefore each somatic cell has two sets of
chromosomes
1. in humans 2n = 46
iii. Homologous chromosomes - are matching pairs of chromosomes
1. 22 pairs of homologous (matching) chromosomes,
called autosomes
2. 1 pair of sex chromosomes, XY or XX
d. Before a cell divides, it must duplicates all of its chromosomes so that
each new cell gets a complete copy of DNA
i. A duplicated chromosome consists of 2 sister chromatids, which
are identical molecules of DNA
III.
Phases of Cell Division
a. The cell cycle consists of two phases:
i. Interphase – cell carrying out daily functions or preparing to
divide
ii. Mitosis- division of the nucleus
b. Phases of Interphase
i. G1 phase – cell spends 90-95% of its time in this phase growing
and carrying out its everyday functions
ii. S-phase - DNA is replicated
iii. G2 phase - final “check point”: make sure everything is ready for
mitosis
c. Phases of Mitosis
i. Prophase
1. Chromatin condenses into chromosomes
2. Centrioles migrate to opposite poles
3. Nuclear membrane breaks down
4. Mitotic spindles form
ii. Metaphase
1. Sister chromatids are aligned in the center of the mitotic
spindle
iii. Anaphase
1. Mitotic spindles shorten pulling chromosomes to opposite
poles
2. Sister chromatids separate becoming daughter
chromosomes
3. The cell begins to elongate
iv. Telophase
1. Chromosomes uncoil into chromatin
2. Spindle breaks down
3. Nuclear membrane reforms
d. Cytokinesis – division of the cytoplasm
i. Original cytoplasmic mass divides resulting in two identical
daughter cells
IV.
Cell division out of control!!!!
a. Cell division is usually under strict control in order to ensure appropriate
proportions. When cell cycle regulation fails, cells start dividing
uncontrollably and result in abnormal masses of dividing cells called
tumors.
b. Types of Tumors
i. Benign – does not invade adjacent tissues, encapsulated
ii. Malignant – invades adjacent tissues
1. Metastasize – cells break away from primary tumor and
travel to other areas of the body
c. Normal cells vs. Cancerous cells
i. Characteristics of Normal Cells
1. Stop dividing after a certain # of divisions
2. Have contact inhibition
3. Differentiated (have a job)
4. Undergo apoptosis if DNA is damaged
ii. Characteristics of Cancer cells
1. Immortal, divide indefinitely
2. No contact inhibition, pile up on each other
3. Non differentiated (no job)
4. Large abnormal nuclei or chromosome numbers
d. Factors that control cell division
i. External signals from neighboring cells
1. Proto-oncogenes – produce proteins that turn on cell
division
a. Mutations in proto-oncogenes (now called
oncogenes) may cause these genes to stay turned on
and produce excess growth stimulating proteins
resulting in uncontrolled cell division
2. Tumor suppressor genes – code for proteins that receive
stop signals from neighboring cells. If mutated they cannot
suppress cell division
ii. Apoptosis – programmed cell death, back up system for cells with
damaged DNA
iii. Telomeres – regions at the end of chromosomes that become
shorter each time the cell divides
1. Keeps cells from becoming immortal
2. Cancer cells have enzyme telomerase which repairs
telomeres
*Optional reading to better understand how cells become cancerous: the article “How
Cancer Arises” posted on Canvas.
Post-Lecture Practice
1. Draw and label the events occurring in the stages of cell division for a cell that is 2n = 4
and give a brief description for each event. Include the phases of interphase, mitosis
(prophase, metaphase, anaphase, telophase), and cytokinesis. Other things you should
include somewhere in your drawing is the labeling of chromatin, homologous chromosomes,
sister chromatids, and daughter chromosomes.