Transcript Ch. 19 The Organization and Control of Eukaryotic Genomes

The Organization and Control
of Eukaryotic Genomes
Ch. 19
AP Biology
Ms. Haut
Structure of Chromatin

Eukaryotes package
their chromosomal
DNA into chromatin
 Based on successive
levels of DNA
packing
Genome Organization at the DNA
Level
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In eukaryotes, most DNA does not encode
protein or RNA, and sequences may be
interrupted by long stretches of noncoding
DNA (introns)

Some of sequences may be present in
multiple copies
Tandemly Repetitive DNA
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~10-25% of total DNA is satellite DNA, short (510 nucleotides) sequences that are tandemly
repeated thousands of times

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Associated with telomeres (ends of
chromosomes)
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
Sequences are not transcribed, function unknown
Important in maintaining integrity of the lagging
strand during DNA replication
Number of genetic disorders caused by
abnormally long stretches of tandemly repeated
nucleotide triplets—fragile X, Huntington’s
disease
Shortening Telomeres


Telomerase
periodically restores
the repetitive
sequence to the ends
of chromosomes
Humans have 2501500 repetitions of
TTAGGG
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Similar among many
organisms--Contain
blocks of G nucleotides
Interspersed Repetitive DNA
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25-40% (in mammals) of
repeated units scattered
about the genome
Alu elements
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There are several
presence/absence
polymorphisms that are
diagnostic for different
human populations
Can be used to infer time
and order of sequence
duplication events
Transposons/Retrotransposons
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“Jumping” genes
Retrotransposons– move within the
genome by means of an RNA
intermediate, a transcript of the
retrotransposon DNA
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To be reinserted, the RNA retrotransposon is
converted back to DNA by the enzyme reverse
transcriptase
Control of Gene
Expression

Cell differentiation —each cell
expresses only a small fraction of
its genes
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Genes are regulated on long term
basis
Transcription enzymes must locate
the right genes at the right time
Uncontrolled or incorrect gene
action can cause serious imbalance
and disease, including cancer
Chromatin Modification affect
Availability of Genes for
Transcription

DNA methylation –addition of –CH3 to
bases of DNA after DNA synthesis
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~5% of Cytosine residues are methylated
Genes not expressed are more heavily
methylated (e.g. Barr bodies)
May explain genomic imprinting where the
maternal or paternal allele of a gene is turned
off at the start of development
Chromatin Modification affect
Availability of Genes for
Transcription
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Histone acetylation –addition of –COCH3 to
certain amino acids of histone proteins
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When acetylated, histones grip DNA less
tightly
Transcription proteins have easier access to
the genes in acetylated regions
Roles of Transcription Factors
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Requires protein-protein interactions to
initiate transcription
Key to efficient transcription are control
elements
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Enhancers—activator protein bind to and
cause “activators” to be brought closer to the
promoter
Repressors—bind silencers which may affect
DNA methylation
Posttranscriptional Mechanisms

Alternative splicing –
different mRNA molecules
are produced from the
same primary transcript
depending on which RNA
segments are treated as
exons and which are
treated as introns
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Controlled by regulatory
proteins
Regulation of mRNA Degradation

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Eukaryotic mRNA can exist in the
cytoplasm for hours or even weeks
Longevity of a mRNA affects how much
protein synthesis it directs (longer viability
= more protein) (e.g. hemoglobin)
Control of Translation
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Binding of repressor protein to 5’-end of
mRNA prevents ribosome attachment
Translation can be blocked by inactivation
of certain initiation factors (occurs during
embryonic development)
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Inactive mRNA can be stored by ovum until
fertilization triggers initiation factors to start
translation
Protein Processing and Degradation
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Polypeptide modification before activation
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Adding phosphate groups or chemical groups such as
sugars
Selective degradation
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Cells attach ubiquitin to mark proteins for destruction
Proteasomes recognize the mark and destroy the
protein
Mutated cell-cycle cyclins that are impervious to
proteasome degradation can lead to cancer
Molecular Biology of Cancer
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Results from genetic changes that affect
the cell cycle
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Can be random and spontaneous
Most likely due to environmental influences
Viral infection
 Exposure to carcinogens (X-rays, chemical agents)
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Leads to activation of oncogenes
Proto-oncogenes
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Genes that normally code for regulatory
proteins controlling cell growth, division
and adhesion
Can be transformed by mutation into an
oncogene
Movement of DNA within the
Genome

chromosomal abberations—placing oncogenes
next to promoters
Burkitt’s
Lymphoma
Gene Amplification
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More copies of oncogenes present in a cell
than normal
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ras gene
Point Mutation
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Slight change in nucleotide sequence
might produce a growth-stimulating
protein that is more active or more
resistant to degradation than the normal
protein
Tumor-Suppressing Genes
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Changes in such genes can code for
proteins that normally inhibit growth can
promote cancer
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p53 gene
Normal function:
Cooperate in DNA repair
 Control cell anchorage
 Play role in cell-signaling pathways that inhibit the
cell cycle
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Tumor-Suppressing Genes
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Faulty tumorsuppressing genes
interfere with normal
signaling pathways
Multiple Mutations
Underlie Cancer
Development
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More than one
somatic mutation is
probably needed to
transform normal cells
into cancerous cells
Breast Cancer
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5-10% of all breast cancer
cases are believed to have
a genetic link.
Of these, ~ 2/3 are caused
by mutations in either
BRCA1 or BRCA2, genes
thought to play a role in
fixing damaged DNA.
~ 50-60 % of individuals
with certain mutations in
either of these two genes
will develop breast cancer
by age 70.
Viral Causes
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15% of human cancer cases worldwide
Some types of leukemia, liver cancer,
cervical cancer
Viruses might:
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add oncogenes to cells
Disrupt tumor-suppressor genes
Convert proto-oncogenes into oncogenes