Chapter 3 – Part D

Cells: The Living Units

3.10 Cell Cycle

● Series of changes a cell undergoes from the time it is formed until it reproduces
● Two major periods of cell cycle:
– Interphase
● Cell grows and carries on its usual activities
– Cell division (mitotic phase)
● Cell divides into two

Interphase
● Period from cell formation to cell division, when cell carries out its routine activities
and prepares for cell division
● During interphase, nuclear material is in uncondensed chromatin state
● Interphase consists of subphases, which include the process of DNA replication

Interphase (cont.)
● Subphases
– Interphase broken into three subphases:
● G1 (gap 1)—vigorous growth and metabolism
– Cells that permanently cease dividing are said to be in G0 phase
● S (synthetic)—DNA replication occurs
● G2 (gap 2)—preparation for division

Interphase (cont.)
● DNA replication
– Prior to division, the cell makes a copy of DNA
– Double-stranded DNA helices unwind and unzip
● Replication fork: point where strands separate
● Replication bubble: active area of replication
● Each strand acts as a template for a new complementary strand
– RNA starts replication by laying down short strand that acts as a primer

Interphase (cont.)
– DNA polymerase attaches to primer and begins adding nucleotides to form new
strand
● DNA polymerase synthesizes both new strands at one time (one leading and
one lagging strand)
– DNA polymerase works only in one direction, so leading strand is synthesized
continuously; however, because lagging strand is “backwards,” it is synthesized
 discontinuously into segments
– Another enzyme, DNA ligase, then splices short segments of discontinuous
lagging strand together

Interphase (cont.)
● End result: two identical “daughter” DNA molecules are formed from the original
● During mitotic cell division, one complete copy will be given to new cell while one is
retained in original cell
● Process is called semiconservative replication because each new
double-stranded DNA is composed of one old strand and one new strand

Cell Division
● Most cells need to replicate continuously for growth and repair purposes
– Skeletal, cardiac, and nerve cells do not divide efficiently; damaged cells are
replaced with scar tissue
● M (mitotic) phase of cell cycle is phase in which division occurs; consists of 2
distinct events:
– Mitosis
– Cytokinesis
● Control of cell division is crucial, so cells divide when necessary, but do not divide
unnecessarily

Cell Division (cont.)

● M phase
– Mitosis is the division of nucleus, in which the duplicated DNA is distributed to
new daughter cells
● Four stages of mitosis ensure each cell receives a full copy of replicated DNA
– Prophase
– Metaphase
– Anaphase
– Telophase

Cell Division (cont.)

● Prophase can be broken into two parts:
1. Early prophase
● Chromatin condenses, forming visible chromosomes
● Each chromosome and its duplicate (called sister chromatids) are held
together by a centromere
● Centrosome and its duplicate begin synthesizing microtubules that push
each centrosome to opposite poles of cell
– Called the mitotic spindle
– Other microtubules called asters radiate from centrosome
Cell Division (cont.)
● Prophase (cont.)
2. Late prophase
● Nuclear envelope breaks up
● Special microtubules attach to specific area on centromeres called
kinetochore and serve to pull chromosomes to center (equator) of cell
● Remaining nonkinetochore microtubules push against each other, causing
poles of cell to move farther apart

Cell Division (cont.)

● Metaphase
– Centromeres of chromosomes are precisely aligned at cell’s equator
– The imaginary plane midway between poles is called metaphase plate

Cell Division (cont.)

● Anaphase
– Shortest of all phases
– Centromeres of chromosomes split simultaneously—each sister chromatid now
becomes a separate chromosome
– Chromosomes are pulled toward their respective poles by motor proteins of
kinetochores
● One chromosome of each original pair goes to opposite poles
– Nonkinetochore microtubules continue forcing poles apart

Cell Division (cont.)

● Telophase
– Begins when chromosome movement stops
– Each set of chromosomes (at opposite ends of cell) uncoils to form chromatin
– New nuclear membranes form around each chromatin mass
– Nucleoli reappear
– Spindle disappears

Cell Division (cont.)

● Cytokinesis
– Begins during late anaphase and continues through mitosis
– Ring of actin microfilaments contracts to form cleavage furrow
– Two daughter cells are pinched apart

Cell Division (cont.)

● Control of cell division
 – “Go” and “Stop” signals direct when a cell should and should not divide
● Go signals include:
– Critical surface-to-volume ratio of cell, when area of membrane becomes
inadequate for exchange
– Chemicals (example: growth factors, hormones)
● Stop signals include:
– Availability of space; normal cells stop dividing when they come into
contact with other cells
» Referred to as contact inhibition

Cell Division (cont.)

● Two groups of proteins are crucial to cell’s ability to accomplish S phase and enter
mitosis:
– Cyclins: regulatory proteins that accumulate during interphase
– Cdks (Cyclin-dependent kinases) that activate cyclins when they bind to them
– Cyclin-Cdk complex in turn activates enzyme cascades that prepare cell for
division
– Cyclins are destroyed after mitotic cell division, and process begins again

Cell Division (cont.)

● Checkpoints are key events in the cell cycle where cell division processes are
checked and, if faulty, stopped until repairs are made
– G1 checkpoint (restriction point) is the most important of the three major
checkpoints
– If cell does not pass, it enters G0, in which no further division occurs

3.11 Protein Synthesis

● DNA is master blueprint that holds the code for protein synthesis
– DNA directs the order of amino acids in a polypeptide
● A segment of DNA that holds the code for one polypeptide is referred to as a gene

3.11 Protein Synthesis

● The code is determined by the specific order of nitrogen bases (Adenine, Guanine,
Thymine, and Cytosine) in the gene
– Code consists of three sequential bases (triplet code)
● Example: GGC codes for amino acid proline, whereas GCC codes for
arginine
– Each triplet specifies the code for a particular amino acid

3.11 Protein Synthesis

● Genes are composed of exons and introns
 – Exons are part of gene that actually codes for amino acids
– Introns are noncoding segments interspersed amongst exons

The Role of RNA

● RNA is the “go-between” molecule that links DNA to proteins
– RNA copies the DNA code in nucleus, then carries it into cytoplasm to ribosomes
● All RNA is formed in nucleus
● RNA differs from DNA
– Uracil is substituted for thymine in RNA
– RNA has ribose instead of deoxyribose sugar
● Three types of RNA:
– Messenger RNA (mRNA)
– Ribosomal RNA (rRNA)
– Transfer RNA (tRNA)

The Role of RNA (cont.)

● Messenger RNA (mRNA)
– Single stranded
– Code from DNA template strand is copied with complementary base pairs,
resulting in a strand of mRNA
● Process is referred to as transcription
– mRNA maintains the triplet code (codon) from DNA

The Role of RNA (cont.)

● Ribosomal RNA (rRNA)
– Structural component of ribosomes, the organelle where protein synthesis occurs
– Along with tRNA, helps to translate message from mRNA into polypeptide

The Role of RNA (cont.)

● Transfer RNA (tRNAs)
– Carrier of amino acid
– Have special areas that contain a specific triplet code (anticodon) that allows
each tRNA to carry only a specific amino acid
– Anticodon of tRNA will complementary base-pair with codon of mRNA at
ribosome, adding its specific amino acid to growing polypeptide chain
● Process is referred to as translation

Protein Synthesis
● Occurs in two steps:
– Transcription
● DNA information coded in mRNA
 – Translation
● mRNA decoded to assemble polypeptides

Transcription
● Process of transferring code held in DNA gene base sequence to complementary
base sequence of mRNA
● Transcription factors (protein complex) activate transcription by:
– Loosening histones from DNA in area to be transcribed so DNA segment can be
exposed
– Binding to special sequence of gene to be transcribed, called promoter (starting
point)
● Occurs only on DNA template strand
– Mediating binding of RNA polymerase, enzyme that synthesizes mRNA, to
promoter region

Transcription (cont.)
● Transcription is broken down into three phases:
1. Initiation
● RNA polymerase separates DNA strands
2. Elongation
● RNA polymerase adds complementary nucleotides to growing mRNA
matching sequence of based on DNA template strand
– Short, 12-base-pair segment where DNA and mRNA are temporarily
bonded is referred to as DNA-RNA hybrid
3. Termination
● Transcription stops when RNA polymerase reaches special termination
signal code

Transcription (cont.)
● Processing of mRNA
– Newly formed mRNA is then edited and processed before translation can begin
● Before processing, it is referred to as pre-mRNA
– Introns are removed by special proteins called spliceosomes, leaving only exon
coding regions

Translation
● Step of protein synthesis where the language of nucleic acids (base sequence) is
translated into the language of proteins (amino acid sequence)
● Process involves:
– mRNA
– Genetic code
– tRNA and ribosomes
 – Translating events
– and sometimes the rough ER

Translation (cont.)
● Genetic code
– Each three-base sequence on DNA (triplet code) is represented by a
complementary three-base sequence on mRNA called codon
– There are 64 possible codons
● 4 bases (A, U, C, G) and 3 places, so 43 = 64
– There are 3 “stop” codons but rest are codons for amino acids
– There are only 20 possible amino acids, so this means that some amino acids
are represented by more than one codon
● Redundancy helps protect against transcription errors

● Role of tRNA
– tRNA binds a specific amino acid at one end (stem); once amino acid is loaded
onto tRNA, molecule is now called an aminoacyl-tRNA
– Anticodon at other end (head) is triplet code that determines which amino acid
will be bound at stem
● Example: tRNA with anticodon UAU will only be able to load a methionine
amino acid to its stem region

Translation (cont.)
– Anticodon of tRNA will bind only to codon on mRNA that is complementary
● Example: if codon is AUA, only a tRNA with anticodon UAU will be able to
bond
– Ribosomes coordinate coupling of mRNA and tRNA
– Ribosomes contain one binding site for mRNA and three binding sites for tRNA:
● Aminoacyl site for incoming aminoacyl-tRNA
● Peptidyl site for tRNA linked to growing polypeptide chain
● Exit site for outgoing tRNA

Translation (cont.)
● Sequence of events in translation
– Translation occurs in three phases that require ATP, protein factors, and enzymes
1. Initiation
2. Elongation
3. Termination

Translation (cont.)
1. Initiation
– Small ribosomal subunit binds to a special initiator tRNA (methionine) and then
 to the mRNA to be decoded
● Ribosome scans mRNA looking for first methionine codon, which is referred
to as the start codon
– When anticodon of initiator tRNA binds to start codon, large ribosomal unit can
then attach to small ribosomal unit forming a functional ribosome
– At end of initiation, initiator tRNA is in P site of ribosome, and A and E sites are
empty

Translation (cont.)
2. Elongation—involves three steps:
● 2a. Codon recognition: tRNA binds complementary codon in A site of
ribosome
● 2b. Peptide bond formation: Ribosomal enzymes transfer and attach
growing polypeptide chain from tRNA in P site over to amino acid of tRNA in
A site
● 2c. Translocation: ribosome shifts down three bases of mRNA, displacing
tRNAs by one position
– tRNA in A site moves into P site
– tRNA in P site moves into E site
– tRNA in E site is ejected from ribosome

Translation (cont.)
2. Elongation (cont.)
– Once A site is empty, a new tRNA can enter, bringing its amino acid cargo, and
whole process starts over
– After a portion of mRNA is “read,” additional ribosomes may attach to already
read part and start another round of translation of same mRNA
● Polyribosome is a multiple ribosome-mRNA complex that produces multiple
copies of same protein

Translation (cont.)
3. Termination
– When one of three stop codons (UGA, UAA, UAG) on mRNA enters A site,
translation ends
– Protein release factor binds to stop codon, causing water to be added to chain
instead of another tRNA
– Causes release of polypeptide chain as well as separation of ribosome subunits
and degradation of mRNA
– Final polypeptide product will be further processed by other cell structures into
functional 3-D protein

Translation (cont.)
● Role of rough ER in protein synthesis
– A short amino acid segment, called the ER signal sequence, present on a
growing polypeptide chain, signals associated ribosome to dock on rough ER
surface
– Signal-recognition particle (SRP) on ER directs mRNA–ribosome complex where
to dock
– Once docked, forming polypeptide enters ER
● Sugar groups may be added to protein, and its shape may be altered
● Protein is then enclosed in vesicle for transport to Golgi apparatus

Summary: From DNA to Proteins

● Complementary base pairing directs transfer of genetic information in DNA into
amino acid sequence of protein
– DNA triplets are coded to mRNA codons
– mRNA codons are base-paired with tRNA anticodons to ensure correct amino
acid sequence
● Anticodon sequence of tRNA is identical to DNA sequence, except uracil is
substituted for thymine

Other Roles of DNA

● DNA codes for other types of RNA:
– MicroRNA (miRNA)
● Small RNAs that can bind to and silence mRNAs made by certain exons
– Riboswitches
● Folded RNAs that act as switches that can turn protein synthesis on or off in
response to certain environmental conditions
– Small interfering RNAs (siRNA)
● Similar to miRNA, but can also be made to silence mRNA from pathogenic
sources such as viruses

3.12 Apoptosis, Autophagy, and Proteasomes

● Cells that have become obsolete or damaged need to be taken out of system
● Autophagy (self-eating) is the process of disposing of nonfunctional organelles and
cytoplasmic bits by forming autophagosomes, which can then be degraded by
lysosomes
● Unneeded proteins can be marked for destruction by ubiquitins
– Proteasomes disassemble ubiquitin-tagged proteins, recycling the amino acids
and ubiquitin

3.12 Apoptosis, Autophagy, and Proteasomes

● Apoptosis, also known as programmed cell death causes certain cells (examples:
cancer cells, infected cells, old cells) to neatly self-destruct
 – Process begins with mitochondrial membranes leaking chemicals that activate
enzymes called caspases
– Caspases cause degradation of DNA and cytoskeleton, which leads to cell death
– Dead cell shrinks and is phagocytized by macrophages

Developmental Aspects of Cells

● All cells of body contain same DNA, but not all cells are identical or carry out same
function
● Chemical signals in embryo channel cells into specific developmental pathways by
turning some genes on and others off
● Development of specific and distinctive features in cells is called cell differentiation

Cell Destruction and Modified Rates of Cell Division

● Organs are well formed and functional before birth, but we need cell division for
growth
● Cell division in adults is needed to replace short-lived cells and repair wounds
● Hyperplasia is accelerated growth that increases cell numbers when needed
● Atrophy is a decrease in size that results from loss of stimulation or use

Cell Aging
● The mechanism of aging is a mystery, but there are several theories:
– Wear and tear theory: lifetime of chemical insults and free radicals have
cumulative effects
– Mitochondrial theory of aging: free radicals in mitochondria diminish energy
production
– Immune system disorders: autoimmune responses, as well as progressive
weakening of immune response

Cell Aging (cont.)

– Genetic theory: cessation of mitosis and cell aging are programmed into genes
● Telomeres are strings of nucleotides that protect ends of chromosomes (like
caps on shoestrings)
● Every time a cell divides, the telomere shortens, so telomeres may act like an
hour-glass on how many times a cell can divide
● Telomerase is an enzyme that lengthens telomeres
– Found in germ cells of embryos but absent in adult cells, except for cancer
cells