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MCON 1: ANATOMY AND PHYSIOLOGY

LECTURE 1: CELLS: THE LIVING UNITS


SOURCE: PPT (CHAPTER 3 PART D)
________________________________________________________________________________________________________

1ST SEMESTER | A.Y. 2022 – 2023

3.10 Cell Cycle • Replication bubble: active area of


replication
• Series of changes a cell undergoes from the time it is
formed until it reproduces • Each strand acts as a template for a
new complementary strand
• Two major periods of cell cycle:
– RNA starts replication by laying down short
– Interphase strand that acts as a primer

• Cell grows and carries on its usual – DNA polymerase attaches to primer and begins
activities adding nucleotides to form new strand

– Cell division (mitotic phase) • DNA polymerase synthesizes both


new strands at one time (one leading
• Cell divides into two and one lagging strand)
Interphase – DNA polymerase works only in one direction, so
leading strand is synthesized continuously;
• Period from cell formation to cell division, when cell carries
however, because lagging strand is
out its routine activities and prepares for cell division
“backwards,” it is synthesized discontinuously
• During interphase, nuclear material is in uncondensed into segments
chromatin state
– Another enzyme, DNA ligase, then splices short
• Interphase consists of subphases, which include the segments of discontinuous lagging strand
process of DNA replication together

• Subphases • End result: two identical “daughter” DNA molecules are


formed from the original
• Interphase broken into three subphases:
• During mitotic cell division, one complete copy will be
• G1 (gap 1): vigorous growth and given to new cell while one is retained in original cell
metabolism
• Process is called semiconservative replication because
• Cells that permanently each new double-stranded DNA is composed of one old
cease dividing are said to strand and one new strand
be in G0 phase

• S (synthetic): DNA replication occurs

• G2 (gap 2): preparation for division

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


• DNA replication occurs; consists of 2 distinct events:

– Prior to division, the cell makes a copy of DNA – Mitosis

– Double-stranded DNA helices unwind and unzip – Cytokinesis

• Replication fork: point where strands • Control of cell division is crucial, so cells divide when
separate necessary, but do not divide unnecessarily
MCON 1: ANATOMY AND PHYSIOLOGY
LECTURE 1: CELLS: THE LIVING UNITS
SOURCE: PPT (CHAPTER 3 PART D)
________________________________________________________________________________________________________

1ST SEMESTER | A.Y. 2022 – 2023

• M phase

1. 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

• 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
• Metaphase
• Centrosome and its duplicate begin
synthesizing microtubules that push – Centromeres of chromosomes are precisely
each centrosome to opposite poles of aligned at cell’s equator
cell
– The imaginary plane midway between poles is
– Called the mitotic spindle called metaphase plate

– Other microtubules called


asters radiate from
centrosome

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
• Anaphase
apart
– 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
MCON 1: ANATOMY AND PHYSIOLOGY
LECTURE 1: CELLS: THE LIVING UNITS
SOURCE: PPT (CHAPTER 3 PART D)
________________________________________________________________________________________________________

1ST SEMESTER | A.Y. 2022 – 2023

– Referred to as contact
inhibition

• 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
• Telophase
– Cyclins are destroyed after mitotic cell division,
– Begins when chromosome movement stops and process begins again

– Each set of chromosomes (at opposite ends of • Checkpoints are key events in the cell cycle where cell
cell) uncoils to form chromatin division processes are checked and, if faulty, stopped until
repairs are made
– New nuclear membranes form around each
chromatin mass – G1 checkpoint (restriction point) is the most
important of the three major checkpoints
– Nucleoli reappear
– If cell does not pass, it enters G 0, in which no
– Spindle disappears further division occurs

• Cytokinesis 3.11 Protein Synthesis

– Begins during late anaphase and continues • DNA is master blueprint that holds the code for protein
through mitosis synthesis

– Ring of actin microfilaments contracts to form – DNA directs the order of amino acids in a
cleavage furrow polypeptide

– Two daughter cells are pinched apart • A segment of DNA that holds the code for one polypeptide
is referred to as a gene

• 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
• Control of cell division
• Genes are composed of exons and introns
– “Go” and “Stop” signals direct when a cell
should and should not divide – Exons are part of gene that actually codes for
amino acids
• Go signals include:
– Introns are noncoding segments interspersed
– Critical surface-to-volume amongst exons
ratio of cell, when area of
membrane becomes • RNA is the “go-between” molecule that links DNA to
inadequate for exchange proteins

– Chemicals (example: – RNA copies the DNA code in nucleus, then


growth factors, hormones) carries it into cytoplasm to ribosomes

• Stop signals include: • All RNA is formed in nucleus

– Availability of space; • RNA differs from DNA


normal cells stop dividing
– Uracil is substituted for thymine in RNA
when they come into
contact with other cells – RNA has ribose instead of deoxyribose sugar
MCON 1: ANATOMY AND PHYSIOLOGY
LECTURE 1: CELLS: THE LIVING UNITS
SOURCE: PPT (CHAPTER 3 PART D)
________________________________________________________________________________________________________

1ST SEMESTER | A.Y. 2022 – 2023

• Three types of RNA: Transcription

– Messenger RNA (mRNA) • Process of transferring code held in DNA gene base
sequence to complementary base sequence of mRNA
– Ribosomal RNA (rRNA)
• Transcription factors (protein complex) activate
– Transfer RNA (tRNA) transcription by:

• Messenger RNA (mRNA) - Loosening histones from DNA in area to be


transcribed so DNA segment can be exposed
– Single stranded
- Binding to special sequence of gene to be
– Code from DNA template strand is copied with transcribed, called promoter (starting point)
complementary base pairs, resulting in a strand - Occurs only on DNA template strand
of mRNA - Mediating binding of RNA polymerase, enzyme
that synthesizes mRNA, to promoter region
• Process is referred to as
transcription • Transcription is broken down into three phases:

– mRNA maintains the triplet code (codon) from 1. Initiation


DNA
• RNA polymerase separates DNA
• Ribosomal RNA (rRNA) strands

– Structural component of ribosomes, the 2. Elongation


organelle where protein synthesis occurs
• RNA polymerase adds
– Along with tRNA, helps to translate message complementary nucleotides to
from mRNA into polypeptide growing mRNA matching sequence of
based on DNA template strand
• Transfer RNA (tRNAs)
• Short, 12-base-pair
– Carrier of amino acid segment where DNA and
mRNA are temporarily
– Have special areas that contain a specific triplet
bonded is referred to as
code (anticodon) that allows each tRNA to carry
DNA-RNA hybrid
only a specific amino acid
3. Termination
– Anticodon of tRNA will complementary base-pair
with codon of mRNA at ribosome, adding its • Transcription stops when RNA
specific amino acid to growing polypeptide chain polymerase reaches special
termination signal code
• Process is referred to as translation

• Occurs in two steps:

– Transcription

• DNA information coded in mRNA

– Translation

• mRNA decoded to assemble


polypeptides
MCON 1: ANATOMY AND PHYSIOLOGY
LECTURE 1: CELLS: THE LIVING UNITS
SOURCE: PPT (CHAPTER 3 PART D)
________________________________________________________________________________________________________

1ST SEMESTER | A.Y. 2022 – 2023

• Processing of mRNA • Example: if codon is AUA, only a


tRNA with anticodon UAU will be able
– Newly formed mRNA is then edited and to bond
processed before translation can begin
– Ribosomes coordinate coupling of mRNA and
• Before processing, it is referred to as tRNA
pre-mRNA
– Ribosomes contain one binding site for mRNA
– Introns are removed by special proteins called and three binding sites for tRNA:
spliceosomes, leaving only exon coding regions
• Aminoacyl site for incoming
Translation aminoacyl-tRNA

• Step of protein synthesis where the language of nucleic • Peptidyl site for tRNA linked to
acids (base sequence) is translated into the language of growing polypeptide chain
proteins (amino acid sequence)
• Exit site for outgoing tRNA
• Process involves:
• Sequence of events in translation
– mRNA
– Translation occurs in three phases that require
– Genetic code ATP, protein factors, and enzymes

– tRNA and ribosomes • Initiation

– Translating events • Elongation

– and sometimes the rough ER • Termination

• Genetic code 1. Initiation

– Each three-base sequence on DNA (triplet – Small ribosomal subunit binds to a special
code) is represented by a complementary three- initiator tRNA (methionine) and then to the
base sequence on mRNA called codon mRNA to be decoded

– There are 64 possible codons • Ribosome scans mRNA looking for


first methionine codon, which is
• 4 bases (A, U, C, G) and 3 places, so referred to as the start codon
43  64
– When anticodon of initiator tRNA binds to start
– There are 3 “stop” codons but rest are codons codon, large ribosomal unit can then attach to
for amino acids small ribosomal unit forming a functional
ribosome
– There are only 20 possible amino acids, so this
means that some amino acids are represented – At end of initiation, initiator tRNA is in P site of
by more than one codon ribosome, and A and E sites are empty
• Redundancy helps protect against 2. Elongation: involves three steps:
transcription errors
2a. Codon recognition: tRNA binds complementary
• Role of tRNA codon in A site of ribosome
– tRNA binds a specific 2b. Peptide bond formation: Ribosomal enzymes
amino transfer and attach growing polypeptide chain from
acid at one end (stem); tRNA in P site over to amino acid of tRNA in A site
once
amino acid is loaded onto 2c. Translocation: ribosome shifts down three
bases of mRNA, displacing tRNAs by one position
tRNA, molecule is now
called tRNA in A site moves into P site
an aminoacyl-tRNA
tRNA in P site moves into E site
– Anticodon at other end (head) is triplet code
that determines which amino acid will be bound tRNA in E site is ejected from ribosome
at stem
– Once A site is empty, a new tRNA can enter,
• Example: tRNA with anticodon UAU bringing its amino acid cargo, and whole
will only be able to load a methionine process starts over
amino acid to its stem region
– After a portion of mRNA is “read,” additional
– Anticodon of tRNA will bind only to codon on ribosomes may attach to already read part and
mRNA that is complementary start another round of translation of same
mRNA
MCON 1: ANATOMY AND PHYSIOLOGY
LECTURE 1: CELLS: THE LIVING UNITS
SOURCE: PPT (CHAPTER 3 PART D)
________________________________________________________________________________________________________

1ST SEMESTER | A.Y. 2022 – 2023

• Polyribosome is a multiple ribosome- • Complementary base pairing directs transfer of genetic


mRNA complex that produces information in DNA into amino acid sequence of protein
multiple copies of same 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

• Termination
Other Roles of DNA
– When one of three stop codons (UGA, UAA,
UAG) on mRNA enters A site, translation ends • DNA codes for other types of RNA:
– Protein release factor binds to stop codon, – MicroRNA (miRNA)
causing water to be added to chain instead of
another tRNA • Small RNAs that can bind to and
silence mRNAs made by certain
– Causes release of polypeptide chain as well as exons
separation of ribosome subunits and
degradation of mRNA – Riboswitches

– Final polypeptide product will be further • Folded RNAs that act as switches that
processed by other cell structures into functional can turn protein synthesis on or off in
3-D protein response to certain environmental
conditions
• Role of rough ER in protein synthesis
– Small interfering RNAs (siRNA)
– A short amino acid segment, called the ER
signal sequence, present on a growing • Similar to miRNA, but can also be
polypeptide chain, signals associated ribosome made to silence mRNA from
to dock on rough ER surface pathogenic sources such as viruses

– Signal-recognition particle (SRP) on ER directs 3.12 APOPTOSIS, AUTOPHAGY, AND PROTEASOMES


mRNA–ribosome complex where to dock
• Cells that have become obsolete or damaged need to be
– Once docked, forming polypeptide enters ER taken out of system

1. Sugar groups may be added to • Autophagy (self-eating) is the process of disposing of


protein, and its shape may be altered nonfunctional organelles and cytoplasmic bits by forming
autophagosomes, which can then be degraded by
2. Protein is then enclosed in vesicle for lysosomes
transport to Golgi apparatus
• Unneeded proteins can be marked for destruction by
ubiquitins

– Proteasomes disassemble ubiquitin-tagged


proteins, recycling the amino acids and ubiquitin

SUMMARY: FROM DNA TO PROTEINS


MCON 1: ANATOMY AND PHYSIOLOGY
LECTURE 1: CELLS: THE LIVING UNITS
SOURCE: PPT (CHAPTER 3 PART D)
________________________________________________________________________________________________________

1ST SEMESTER | A.Y. 2022 – 2023

• 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: a 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

– 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)

• Everytime 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

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