Download Chapter 4 Genetics Cellular Function

Chapter 4
Genetics
And
Cellular
Function
4-1
Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Genetics and Cellular Function
• Genes and nucleic acids
• Protein synthesis and secretion
• DNA replication and the cell cycle
4-2
Organization of the Chromatin
• Threadlike chromatin =
chromosomes = 46 DNA
molecules and associated
proteins
• Nondividing state = DNA
molecules compacted
– coiled around core particle (histone
protein)
– zig-zagged, looped and coiled onto
itself
• Preparing to divide
– DNA copies itself to form 2 parallel
sister chromatids
4-3
DNA Structure: Twisted Ladder
DNA molecule described as double helix.
4-4
Nucleotide Structure
• DNA = polymer of
nucleotides
• Each nucleotide consist of
– phosphate group
– sugar
• ribose (RNA)
• deoxyribose (DNA)
– nitrogenous base
• in this picture = adenine
4-5
Nitrogenous Bases
• Purines - double ring
– guanine
– adenine
• Pyrimidines - single
ring
– uracil - RNA only
– thymine - DNA only
– cytosine – both
• DNA bases =CTAG
• RNA bases = CUAG
4-6
Complementary Base Pairing
• Nitrogenous bases
united by hydrogen
bonds
• DNA base pairings
– A-T and C-G
• Law of complementary
base pairing
– one strand determines
base sequence of other
Segment of DNA
4-7
DNA Function
• Code for protein synthesis
• Gene - sequence of DNA nucleotides
that codes for one protein
• Genome - all the genes of one person
– humans have estimated 30-35,000 genes
– other 98% of DNA noncoding – “junk” or
regulatory
4-8
RNA: Structure and Function
• RNA smaller than DNA (fewer bases)
– transfer RNA (tRNA) 70 - 90 bases
– messenger RNA (mRNA) over 10,000 bases
– DNA has over a billion base pairs
• Only one nucleotide chain (not a helix)
– ribose replaces deoxyribose as the sugar
– uracil replaces thymine as a nitrogenous base
• Essential function
– interpret DNA code
– direct protein synthesis in the cytoplasm
4-9
• DNA directs the synthesis of all cell
proteins
– including enzymes that direct the
synthesis of nonproteins
• Different cells synthesize different
proteins
– dependent upon differing gene activation
4-10
DNA Replication 1
4-11
DNA Replication 2
• Law of complimentary base pairing allows
building of one DNA strand based on the
bases in 2nd strand
• Steps of replication process
– DNA helicase opens short segment of helix
• replication fork is point of separation of 2 strands
– DNA polymerase assembles new strand of
DNA next to one of the old strands
• 2 DNA polymerase enzymes at work
simultaneously
4-12
DNA Replication 3
• Semiconservative replication
– each new DNA molecule contains one new
helix and one conserved from parent DNA
• Additional histones made in cytoplasm
• Each DNA helix winds around histones to
form nucleosomes
• 46 chromosomes replicated in 6-8 hours by
1000’s of polymerase molecules
4-13
Errors and Mutations
• Error rates of DNA polymerase
– in bacteria, 3 errors per 100,000 bases copied
• Proofreading and error correction
– a small polymerase proofreads each new DNA
strand and makes corrections
– results in only 1 error per 1,000,000,000 bases
copied
• Mutations - changes in DNA structure due to
replication errors or environmental factors
– some cause no effect, some kill cell, turn it
cancerous or cause genetic defects in future
generations
4-14
Protein Synthesis
4-15
Genetic Control of Cell Action
through Protein Synthesis
4-16
Protein Synthesis
• Transcription
– messenger RNA (mRNA) is formed from
an activated gene
– mRNA migrates to cytoplasm
• Translation
– mRNA code is “read” by ribosomal RNA
as amino acids are assembled into a
protein molecule
– transfer RNA delivers the amino acids to
the ribosome
4-17
Genetic Code
• System that enables the 4 nucleotides
(A,T,G,C) to code for the 20 amino acids
• Base triplet:
– found on DNA molecule (ex. TAC)
– nucleotides that stand for 1 amino acid
• Codon:
– “mirror-image” sequence of nucleotides found in
mRNA (ex AUG)
– 64 possible codons (43)
• often 2-3 codons represent the same amino acid
• start codon = AUG
4-18
• 3 stop codons = UAG, UGA, UAA
Transcription
• Copying instructions from DNA to RNA
– RNA polymerase binds to DNA
• at site selected by chemical messengers from
cytoplasm
– opens DNA helix and transcribes bases from
1 strand of DNA into pre-mRNA
• if C on DNA, G is added to mRNA
• if A on DNA, U is added to mRNA, etc.
– rewinds DNA helix
• Pre-mRNA is unfinished
– “nonsense” (introns) removed by enzymes
– “sense” (exons) reconnected and exit
nucleus
4-19
Alternative Splicing of mRNA
• One gene can code for more than one
protein
• Exons can be spliced together into a
variety of different mRNAs.
4-20
Translation of mRNA
• mRNA begins with leader sequence
– binding site for ribosome
• Start codon AUG
4-21
Steps in Translation of mRNA
• Converts alphabet of nucleotides into a
sequence of amino acids to create a
specific protein
• Ribosome in cytosol or on rough ER
– small subunit attaches to mRNA leader sequence
– large subunit joins and pulls mRNA along as it
“reads” it
• start codon (AUG) where protein synthesis begins
– small subunit binds activated tRNA with
corresponding anticodon
– large subunit enzyme forms peptide bond
4-22
Steps in Translation of mRNA
• Growth of polypeptide chain
– next codon read, next tRNA attached,
amino acids joined, first tRNA released,
process repeats and repeats
• Stop codon reached and process
halted
– polypeptide released and ribosome
dissociates into 2 subunits
4-23
Transfer RNA (tRNA)
• Activation by ATP binds specific amino acid and
provides necessary energy to join amino acid to
growing protein molecule
• Anticodon binds to complementary codon of
4-24
mRNA
Polyribosomes
4-25
Polyribosomes and Signal
Peptides
• Polyribosome
– cluster of 10-20 ribosomes reading mRNA at one
time
– horizontal filament - mRNA
– large granules - ribosomes
– beadlike chains projecting out - newly formed
proteins
• takes 20 seconds to assemble protein of 400 amino
acids
• cell may produce > 150,000 proteins/second
• Signal peptide = beginning of chain of amino
acids
– determines protein’s destination within cell
4-26
DNA and Peptide Formation
4-27
Chaperones and Protein
Structure
• Newly forming protein molecules must
coil or fold into proper 2nd and tertiary
molecular structure
• Chaperone proteins
– prevent premature folding, assist in proper
folding and escort protein to final
destination
4-28
Protein Packaging and Secretion
4-29
Posttranslational Modification
in Rough ER
• Proteins destined for secretion or packaging are
assembled on rough ER and sent to Golgi
complex
• Signal peptide
– drags new protein from ribosome through pore into
cisterna of ER
• Posttranslational modification of protein in ER
– remove some amino acids, fold the protein adding
disulfide bridges or adding carbohydrates
• Rough ER pinches off transport vesicles
– fuse with and empty into nearest Golgi complex
4-30
Posttranslational Modification
in Golgi Complex
• Protein modified in cisterna, passed to
next cisterna
• Last golgi cisterna releases finished
product as membrane bound vesicles
– secretory vesicles
• migrate to plasma membrane and release
product by exocytosis
– lysosomes
• vesicles that remain in cell
4-31
Cell Cycle
• G1 phase, the first gap phase
– accumulates materials needed
to replicate DNA
• S phase, synthesis phase
– DNA replication
• G2 phase, second gap phase
– replicates centrioles
– synthesizes enzymes for division
• M phase, mitotic phase
– nuclear and cytoplasmic division
• G0 phase, cells that have left the cycle
• Cell cycle duration varies between cell types
4-32
Mitosis
• one cell divides into 2 daughter cells
with identical copies of DNA
• Functions of mitosis
– embryonic development
– tissue growth
– replacement of dead cells
– repair of injured tissues
• Phases of mitosis (nuclear division)
– prophase, metaphase, anaphase, telophase
4-33
Mitosis
4-34
Mitosis: Prophase 1
• Chromatin coils into genetically
identical, paired, sister
chromatids
– each chromatid contains a DNA
molecule
– remember: genetic material (DNA)
was doubled during S phase of
interphase
• Thus, there are 46
chromosomes with 2
chromatids/chromosome and 1
molecule DNA per chromatid.
4-35
Prophase
2
• Nuclear envelope disintegrates
• Centrioles sprout microtubules that push them apart
and towards each pole of the cell
– spindle fibers grow towards chromosomes
• attach to kinetochore on side of centromere
– spindle fibers pull chromosomes towards cell equator
4-36
metaphase
•Chromosomes line up on one equator
•Mitosis spindles finished
spindle fibers (microtubules) attach centrioles to long centromere
shorter microtubules anchor centrioles to plasma membrane (aster)
4-37
anaphase
•Enzyme splits 2 chromatids apart at centromere
•Daughter chromosomes move towards opposite poles of cells
with centromere leading the way
•motor proteins in kinetochore move centromeres along spindle
fibers as fibers are disassembled
4-38
telophase
• New nuclear envelopes formed by
rough ER
• Chromatids uncoil into chromatin
• Mitotic spindle breaks down
• Nucleus forms nucleoli
4-39
Cytokinesis
• Division of cytoplasm into 2 cells
– overlaps telophase
• Myosin pulls on microfilaments of actin
in the membrane skeleton
– creates crease around cell equator called
cleavage furrow
• Cell pinches in two
– interphase has begun
4-40
Timing of Cell Division
Cells divide when:
• Have enough cytoplasm for 2 daughter
cells
• DNA replicated
• Adequate supply of nutrients
• Growth factor stimulation
• Open space due to neighboring cell death
Cells stop dividing when:
• Loss of growth factors or nutrients
• Contact inhibition
4-41
Chromosomes and Heredity
• Heredity = transmission of genetic
characteristics from parent to offspring
– karyotype = chart of chromosomes at metaphase
• 23 pairs homologous chromosomes in somatic
cells (diploid number of chromosomes)
– 1 chromosome inherited from each parent
– 22 pairs called autosomes
– one pair of sex chromosomes (X and Y)
• normal female has 2 X chromosomes
• normal male has one X and one Y chromosome
• Sperm and egg contain only 23 chromosomes
– fertilized egg has diploid number of chromosomes
4-42
Karyotype of Normal Male
4-43