Lesson 4: Chapter 4: Genes & Cellular Function

Deoxyribonucleic acid (DNA)

- long, thread-like molecule with uniform diameter, but varied length

- 46 DNA molecules (chromosomes) in nucleus of most human cells

- 23 chromosomes for maternal side (oocyte); 23 from paternal (sperm)

- avg. human DNA molecule about 2 inches long

nucleotide consist of three components

1. a sugar - deoxyribose

2. a phosphate group

3. a nitrogenous base (DNA bases: A, T, C, G)

essential function of DNA

to carry instructions (genes) for the synthesis of proteins

gene

segment of DNA coding for the synthesis of a specific protein

Humans have about 20,00 genes but how much is actually coding DNA

~2% = coding DNA

~98% = noncoding DNA (plays role in chromosome structure, regulates gene activity)

chromatin

fine filamentous DNA material complexed with proteins called histones

forms complex loops and coils

how many chromosomes are in most cells

46

chromosomes

tightly packed DNA; usually found during mitosis when chromatin condenses as it becomes tightly packed

histones

-proteins around which DNA winds

-cluster in groups of eight molecules

-DNA molecule winds around the cluster (like thread around a spool) (nucleosome)

nucleosome

DNA wrapped around histones

DNA replication

the copying of DNA to make another molecule of DNA

DNA replication occurs in what fashion

semi-conservative

sister chromatids

each chromosome consists of two parallel filaments of identical DNA

centromere

chromatids are joined at the constricted version of this

kinetochores

protein plaques on each side of centromere, play a role in cell division

Ribonucleic acids (RNAs)

- ribose sugar

- A, U, G, C bases

- single nucleotide chain

- smaller than DNA

- functions mainly in cytoplasm

three RNAs are important for protein synthesis

messenger RNA (mRNA)

ribosomal RNA (rRNA)

transfer RNA (tRNA)

gene (current def.)

an information-containing segment of DNA that codes for the production of a molecule of RNA that most often plays a role in synthesizing one or more proteins

messenger RNA (mRNA)

when a gene is activated this is made; serves as a code for a particular protein

transcription

DNA → mRNA (copying genetic instructions from DNA to mRNA)

occurs in nucleus

translation

mRNA → protein (nucleotide language in mRNA is converted into amino acid language)

occurs in cytoplasm

RNA polymerase

enzyme utilized in transcription that

1. binds to transcription start sequence in DNA

2. opens up the DNA double helix

3. reads the nitrogenous bases from one strand of DNA to build the complementary strand of mRNA

4. rewinds DNA helix behind it (allows gene to be transcribed by several polymerase molecules)

terminator

stop sequence on DNA at the end of a gene

pre-mRNA

immature RNA produced by transcription that will undergo processing

pre-mRNA processing

enzymes remove introns and splice exons together

(introns = noncoding, exons = will be expressed)

three main participants in translation

1. Messenger RNA (mRNA)

2. Transfer RNA (tRNA)

3. Ribosomes

messenger RNA (mRNA)

- carries genetic code from nucleus to cytoplasm

- has protein cap that is recognition site for ribosome

transfer RNA (tRNA)

- delivers single amino acid to ribosome

- contains an anticodon

anticodon

series of 3 nucleotides that are complementary to the mRNA codon

codon

series of 3 nucleotides on mRNA

ribosomes

- organelles that read the message and build a peptide chain

- contain a large subunit and a small subunit

- free in cytosol, on rough ER, and on nuclear envelope

- The E site, P site, and A site are involved in translation

three main steps in translation

1. initiation

2. elongation

3. termination

initiation

- ribosome assembles with mRNA in the cytosol

- small subunit binds the leader sequence of mRNA and reads the mRNA strand unit it reaches the start codon (AUG), the first tRNA brings the first amino acid (methionine) and then the large ribosomal subunit attached

- protein synthesis begins (the first tRNA is in the P site)

elongation

- next tRNA with its amino acid arrives, binds to A site

- ribosome creates peptide bond between first and second amino acids

-ribosome moves down mRNA by one codon (3 nucleotides), so growing peptide is not attached to tRNA in P site

- process continues and peptide grows

Termination

- ribosome reaches a stop codon on mRNA

- the A site binds a protein called a release factor

- ribosome disassembles and dissociates from the mRNA

Making proteins for packaging or export

- proteins destined for lysosomes or secretion are modified by ER

- ribosome docks on ER and synthesizes protein into ER cistern

- the rough ER modifies and packages protein into transport vesicles

polyribosomes

multiple ribosomes in clusters; can translate the same mRNA molecule simultaneously

process of protein processing and secretion

1. post-translational modification

2. protein pinches off from rough ER in transport vesicle

3. clusters of vesicles fuse and form a new Golgi cistern, the cis cistern

4. new cistern migrates through Golgi to opposite (trans) face

5. the trans cistern breaks up into vesicles containing cell product

6. some vesicles become lysosomes, others become secretory vesicles that fuse with membrane to release their contents

process of protein processing and secretion: post-translational modification

- protein assembled on ER surface threads itself through a pore in the rough ER membrane into its cistern

- enzymes in the rough ER modify the protein - remove some amino acid segments, fold the protein, stabilize with disulfide bridges, add carbohydrates, etc.

genes can be turned on and off

- cells can permanently turn off some genes

- cells can turn genes on only when needed

cells can permanently turn off some genes

Ex. liver cells turn off hemoglobin genes

cells can turn genes on only when needed

- the level of gene expression can vary from day to day or hour to hour

- this can be controlled by chemical messengers such a hormones

- Ex. in response to prolactin, mammary gland cells turn on gene for casein protein only when breast milk is produced

gene regulation: Casein synthesis and secretion

1. hormone prolactin binds to receptors on membrane of mammary cell

2. receptors trigger activation of a regulatory protein (transcription activator) in the cytoplasm

3. regulatory protein moves into the nucleus and binds to the DNA near the casein gene

4. the binding enables RNA polymerase to bind to the gene and transcribe it, producing the mRNA for casein

5. the casein mRNA moves to the cytoplasm, bind to ribosomes, start translation, and ribosomes move to and attach to the rough ER complete translation

7. the secretory vesicles release the casein by exocytosis, and it becomes part of the milk

Synthesizing compounds other than proteins

- genes may greatly affect such complex outcomes as behavior, aggression, and sex drive

- cells synthesize glycogen, fat, steroids, phospholipids, pigments, and other compounds

genes may greatly affect such complex outcomes such as behavior, aggression, and sex drive

expression of genes can directly control the amount of structural proteins (ex. cytoskeleton elements) or protein secretions

cells synthesize glycogen, fat, steroids, phospholipids, pigments, and other compounds

- no genes for these products, but their synthesis is under INDIRECT genetic control

- they are produced by enzymatic reactions, and enzymes are proteins encoded by genes

-Ex. production of testosterone (a steroid)

DNA replication

the process of a cell duplicating its DNA it preparation of division so that it can give a complete copy of all its genes to each daughter cell

four steps of DNA replication

1. unwinding the helix from the histones

2. unzipping small portion of helix by DNA helicase enzyme; separates the strands, forming a replication fork

3. enzyme called DNA polymerase moves along each strand, reads the exposed bases, and synthesizes complementary strands

4. new histones synthesized, used to organize new DNA strands into nucleosomes

3rd step DNA replication: enzyme called DNA polymerase moves along each strand, reads the exposed bases, and synthesizes complementary strands

- one the new but discontinued strand, segments are connected by DNA ligase enzyme

- semiconservative replication

DNA ligase

in DNA replication, connects segments on the new but discontinued strand

semiconservative replication

each new DNA molecule contains old (parental) DNA and newly synthesized DNA

cell cycle

Interphase + miotic phase

interphase subphases

First gap phase (G1)

Synthesis phase (S)

Second gap phase (G2)

miotic phase subphases

prophase

metaphase

anaphase

telophase

the majority of a cells life is spent in which phase

interphase (mitosis occupies small segment in comparison)

Why is cytokinesis NOT a phase

It starts during late anaphase and continues through telophase

G1: first gap phase

interval between cell division and DNA replication

cell carries out normal tasks and synthesizes proteins and materials for next phase

S: synthesis phase

cell replicates all nuclear DNA and duplicates centrioles

G2: second gap phase

interval between DNA replication and cell division

cell repairs DNA replication errors, grows, and synthesizes enzymes that control cell division

miotic phase

refers to the events during nuclear division

cell replicated its nucleus

cytokinesis

cytokinesis

not a phase of mitosis, occurs during late anaphase of mitosis and causes cell to pinch in two to form new daughter cells

G0 (G zero) phase

- cells that have left the cycle and cease dividing for a long time (or permanently)

- typically once a cell enters, it remains there (ex. skeletal muscle cells, cardiac muscle cells, neurons)

Why will stem cells never enter G0

since the need to undergo mitosis to replace worn out tissue (ex. epithelial stem cells lining the skin, digestive tract, etc.)

Mitosis

cell division resulting in two genetically identical daughter cells

meiosis

produces eggs and sperm cells containing half the genetic information

functions of mitosis

- development of individual from fertilized egg to about 50 trillion cells

- growth of all tissues and organs after birth, replacement of cells that die, and repair of damaged tissues

prophase

- genetic material condenses into compact chromosomes (easier to distribute)

- 46 chromosomes (two chromatids per chromosome)

- nuclear envelope disintegrates

- centrioles sprout spindle fibers (long microtubules)

spindle fibers

- push centriole pairs apart

- attach to kinetochores of centromeres

metaphase

- chromosomes are aligned on cell equator

- spindle fibers form lemon-shaped array called the mitotic spindle

- shorter microtubules from centrioles complete a starlike aster which anchors itself to inside of cell membrane

anaphase

- enzyme cleaves two sister chromatids apart at centromere

- single-stranded daughter chromosomes migrate to each pole of the cell as motor proteins in kinetochores crawl along spindle fibers

telophase

- chromosomes cluster on each side of the cell

- rough ER makes new nuclear envelope around each cluster

-chromosomes uncoil to chromatin

-miotic spindle disintegrates

-each nucleus reforms nucleoli

cytokinesis

- division of cytoplasm into two cells'

- the start of cytokinesis can be seen in late anaphase and extends through telophase

- achieved by myosin protein pulling on actin in the terminal web of cytoskeleton

myosin protein pulling on actin in the terminal web of cytoskeleton

- creates crease called the cleavage furrow around the equator of the cell

- cell pinched in two; two daughter cells with the same genetic information are formed

cells divide when:

-they have enough cytoplasm for two daughter cells

- they have replicated their DNA

- they have adequate supply of nutrients

- they are stimulated by growth factors (chemical signals), increase in M-phase promoting factor (MPF) in the cell

- neighboring cells die, opening up space

cells stop dividing when:

- nutrients or growth factors are withdrawn

- they snugly contact neighboring cells

- they experience contact inhibition

contact inhibition

the cessation of cell division in response to contact with other cells

malignant tumors

cause cancer by spreading into surrounding tissue (invasion)

malignant tumor characteristics

- grow rapidly

- tend to metastasize

- may stimulate tumor angiogenesis

- distinguished from slow growing, encapsulated benign tumors

metastasize

give off cells that spread and seed the growth of tumors elsewhere (secondary tumors) (primary tumor - origin of the tumor)

tumor angiogenesis

growth of blood vessels by energy-hungry tumors

lethal effects of cancer

- replace functional tissue in vital organs (often invade blood vessels, lung tissue, or brain tissue)

- tumors can put pressure on organs, blocking their normal function

- weaken one’s immunity

- open the door for opportunistic infections

- steal nutrients from the rest of the body (cachexia)

cachexia

severe wasting away of depleted tissues