UNIT IV - DNA & CELL DIVISION

Big Campbell – Ch 12, 13, 16Baby Campbell – Ch 8, 10.1-10.5

I. INTRODUCTION TO DNA• Genome

o All of an organism’s DNAo Provides working instructions for cell

through ______________________o Must be copied prior to cell division

• Chromosome o Single molecule of DNA wrapped in

protein. Proteins maintain chromosome structure & control DNA activitySomatic cells

Gametes

• Chromatin o Term used to describe fine strands of

uncoiled DNA

II. A CLOSER LOOK AT DNA• Discovery of DNA

o Early 1900s – Scientists determined genes determined inherited characteristics. Also realized chromosomes were composed of DNA & protein.

o Griffith (1928) – Studied 2 strains of bacteria. Determined that pathogenicity could be transferred when living non-pathogens were exposed to remains of dead pathogens.

o Avery (1944) – Identified “transforming substance” as DNA

o Hershey & Chase (1952) – Used radioactively-viruses that infect bacteria - known as bacteriophages. Virus is made up of DNA & protein – Hershey & Chase proved it was the DNA component that was injected into host cell and used to make new virus particles.

o Rosalind Franklin (late 1950s) – Produced x-ray crystallography image of DNA; “borrowed” by Watson & Crick

II. A CLOSER LOOK AT DNA, cont• Watson & Crick

o Realized DNA was a helix composed of 2 nucleotide strands

o Franklin suggested backbone of DNA was composed of alternating sugar-phosphate molecules

o Watson & Crick determined interior of DNA was made up of paired N-bases

o Eventually deduced bases always paired a specific way

• Chargaff – Chemically proved the same base-pairing rules that Watson & Crick proved structurally

II. A CLOSER LOOK AT DNA, cont

• Monomers of DNAo Nucleotideso Composed of

Pyrimidines

Purines

II. A CLOSER LOOK AT DNA, cont

• Structure of DNA Double helix Strand of nucleotides held

together by covalent bonds Nitrogen bases held

together with hydrogen bonds

2 nucleotide strands are

antiparallel Each strand has a 3’ end

(terminus) and a 5’end; named for carbon on deoxyribose

II. A CLOSER LOOK AT DNA, cont

III. DNA REPLICATION• DNA Replication

o Prior to cell division, DNA must be replicatedo Known as semiconservative model of replication

Meselson-Stahl Experiment

III. DNA REPLICATION, cont.

• Chromatids Two identical DNA

moleculesResult of replicationTerm is only used when

identical DNAs are physically attached; described as one chromosome made up of two sister chromatids

Centromere – Site where sister chromatids are most closely attached

III. DNA REPLICATION, cont.

• The Steps of Replication: DNA helicase unwinds the DNA double helix Replication begins at specific points on the DNA molecule known as

origins of replication. The Y-shaped region where new strands of DNA are elongating are called replication forks

III. DNA REPLICATION, cont. As DNA is “unzipped”, single-strand binding proteins hold the DNA

open A topoisomerase relieves tension creating by unwinding of DNA by

making cuts, untwisting, & rejoining the nucleotide strand. DNA polymerase can only add nucleotides to an already-existing

strand so an RNA primer is synthesized to get replication going

III. DNA REPLICATION, cont. DNA polymerases add complementary nucleotides to each side

of the DNA molecule. DNA polymerase can only add nucleotides to the 3’ end of the growing strand, so the daughter DNA is synthesized 5’ – 3’; therefore, only one side of the DNA (3’ – 5’) molecule can be replicated as a continuous strand. Known as the leading strand.

III. DNA REPLICATION, cont.• Synthesis of lagging strand

To synthesize the other new strand of DNA, DNA polymerase must work away from the replication fork. Leads to synthesis of short pieces of DNA known as Okazaki fragments.

DNA ligase binds fragments together to form a continuous strand of nucleotides.

• Proofreading & Repair DNA Polymerase proofreads nucleotides as they are added

III. DNA REPLICATION, cont.

An Overview of Replication

III. DNA REPLICATION, cont.• Telomeres

5’ ends of daughter strands cannot be completed because DNA polymerase can only add nucleotides to the 3’ end

Results in shorter and shorter DNA molecules with jagged ends To protect genetic integrity, ends of chromosomes do not contain genes

– instead there are nucleotide sequences known as telomeres Contain nucleotide repeat sequences Telomeres shorten each time cell divides - limits the number of times a

cell can divide; thought to protect organism from cancer Telomerase – Enzyme produced by stem cells, cancer cells that restores

telomere length

IV. ASEXUAL REPRODUCTION

•Cell Theory Virchow

•Cell Cycle

Single-celled Organisms

Multicellular Organisms

V. PROKARYOTIC CELL DIVISION

• Known as binary fissiono Asexual reproductiono Much shorter than euk cell

cycleSingle chromosome

replicatesEach copy begins moving to

opposite ends of cellCell elongatesWhen bacterium is 2X

original size, cell membrane pinches inward

Cell wall deposited2 identical cells produces

VI. EUKARYOTIC CELL CYCLE• Can be divided into:

VI. EUKARYOTIC CELL CYCLE, cont• Interphase

– Portion of cell cycle in which cell is carrying out normal activities.

– Approx 90% of normal cell cycle is spent in interphase.

– DNA found in chromatin form– 3 sub-phases

• G1 – Period of time following cell division in which cell is growing to normal size. Protein production, metabolism high.

• S – DNA replication. Known as “point of no return”. Chromosome now consists of 2 sister chromatids.

• G2 – Preparation for division; replication of centrioles in animal cells

VI. EUKARYOTIC CELL CYCLE, cont

• Mitosis – Nuclear division – Requires all the

cells energy, resources

– Last step is cytokinesis – splitting of the cell

VI. EUKARYOTIC CELL CYCLE, cont

VI. EUKARYOTIC CELL CYCLE, cont

VI. EUKARYOTIC CELL CYCLE, cont

• Cytokinesis in Animal & Plant Cells

VI. EUKARYOTIC CELL CYCLE, cont

VII. CONTROL OF THE CELL CYCLE, cont

• Internal Signalso Three major checkpoints in

cell cycleo Regulated by enzymes

known as cyclin-dependent kinases or Cdks; activated when bound to proteins known as cyclins

o Cdk concentration fairly constant; cyclin concentration is critical factor

o Most important checkpoint is the G1 checkpoint. If there is no signal, cell exits cell cycle and switches to G0

VII. CONTROL OF THE CELL CYCLE• External Signals

o Growth FactorsProteins released by certain cells

that stimulates other cells to divide.

Cells stop dividing when growth factor is depleted.

Examples include erythropoetin, interleukin

o Density-dependent Inhibition Results from crowded conditionsWhen one cell touches another,

cell division stops

o Anchorage DependenceMost cells must be in contact with

solid surface to divide

VII. CONTROL OF THE CELL CYCLE, cont

• Cell Cycle Out of Control = CANCERo Cancer cells do not respond to normal cell cycle controls

Apoptosis – Programmed cell deatho Uncontrolled growtho Deprive normal cells of nutrientso Named after type of cells affected

Carcinoma – originate in linings & coverings; for example, skin or lining of digestive tract

Sarcoma – originate in support tissues; for example, bone and muscle

Lymphoma/Leukemia – originate in blood-forming tissues; for example, bone marrow, spleen, lymph nodes

VII. CONTROL OF THE CELL CYCLE, conto Tumor – Mass of abnormal cells

Benign – Mass remains at original siteMalignant – Mass spreads to other parts of the bodyMetastasis – Separation of cancer cells from tumor; travel

through circulatory system

VIII. MEIOSIS

• Somatic Cellso Body cellso Human somatic cells contain 46 chromosomes, 23 from

mom, 23 from dado 2n or diploido Matched pairs of chromosomes called homologous pairs.

Each chromosome making up a homologous pair is known as a homologue. Both carry genes for same traits. The location of a gene on a chromosome is known as a locus. Autosomes – Human somatic cells contain 44 autosomesSex chromosomes – 2 per somatic cell

XX = XY =

VIII. MEIOSIS, cont• Gametes

o Egg and sperm cellso Haploid or no Contain 23 chromosomeso In fertilization, haploid (n)

sperm fuses with haploid (n) egg → diploid (2n) zygote

• Meiosiso Occurs in ovaries, testeso DNA replicated once, cell

divides twiceo Produces 4 cells with ½ the

original chromosome number

VIII. MEIOSIS, cont

VIII. MEIOSIS, cont

VIII. MEIOSIS, cont• Nondisjunction – Failure of chromosomes to separate

properly in meiosis

IX. MEIOSIS vs MITOSIS

X. GENETIC VARIATION

X. GENETIC VARIATION, cont

• Crossing Over o Further increases genetic

variabilityo Occurs during prophase I

when tetrads are formingo Piece of one sister

chromatid breaks off & exchanges places with piece of sister chromatid of homologue

o Known as chiasmao Occurs very frequently