III. Cancer results from genetic changes that affect cell cycle control
A. Mutations – changes to the nucleotide sequence that occur randomly or
result from environmental factors
a. When they affect growth factors, receptors, and intracellular signaling
molecules they can affect the cell cycle and lead to cancer
b. Some viruses turn cells cancerous with the implementation of their
viral genome
B. Types of genes associated with cancer
a. Proto-oncogenes – genes that code for normal proteins that stimulate
cell growth and division
i. Ex. Ras – a G protein that relays signal from growth factor at
the cell surface to a cascade of protein kinases
b. Oncogenes – mutated genes that increase the amount of product or its
activity and cause cancer
i. Ex. Mutated Ras gene = hyperactive Ras protein and cell
division even in the absence of growth factor
c. Causes of the switch:
i. Movement of DNA in the genome (transposition)
ii. Amplification of the proto-oncogenes
iii. Point mutations in control element or protooncogene
d. Increasing activity of the cell cycle OR limiting it’s inhibition will cause
uncontrolled division and growth
i. Mutations in tumor suppressor genes allow less restricted
division
ii. Ex. P53 protein – when DNA is damaged it activates p53
protein which acts as a transcription factor for proteins that
inhibit the cell cycle, are involved in DNA repair, or are
involved in programmed cell death (apoptosis)
iii. Mutated p53 prevents the production of these products for
inhibition/repair/destruction THUS defective genes and cells
are more likely to survive and proliferate.
C. Multistep model for cancer development
a. If cancer results from an accumulation of mutations, and mutations
occur throughout our lifetime, then the longer we live, the more likely
we are to develop cancer.
IV. Eukaryotic genomes can have many noncoding DNA sequences in addition to
genes
A. Eukaryotic chromosomes have more non-coding DNA in comparison with
prokaryotic chromosomes
a. Some of this noncoding DNA falls within transcriptional units (Ex.
Introns and regulatory sequences [like the promoter and terminator
region]
b. Some of this noncoding DNA falls between transcriptional units (Ex.
Repetitive DNA sequences like transposable elements or simple
sequence DNA)
i. Transposable elements: gene segments that can move
1. Transposons – DNA moves and is inserted into the
genome
a. May be copied or cut, and inserted elsewhere
2. Retrotransposons – RNA transcript is translated to
make reverse transcriptase which converts RNA
transcript back to DNA which is inserted into the
genome
a. Employs the use of the reverse transcriptase
enzyme (also seen in retroviruses)
ii. Simple sequence DNA – short repeating “satellite” sequences
which have a different density and play a role in the telomeres
and centromeres
B. Eukaryotic genomes also contain multigene families
a. Repeating identical gene sequences produce high levels of RNA
products required for cellular function Ex. rRNA
b. May be comprised of non-identical but related genes
i. Pseudogenes may also be present – similar to the functional
genes in the multigene family but through mutation have a loss
of function
c. Indication of the evolution of genomes – how information can be split,
changed, or moved in the genome over time through – we can
interpret the evolution of genomes by comparing the nucleotide and
amino acid sequences in order to determine relatedness
i. Duplication – copies of genetic info are inserted into the
genome – these copies end up in different places and diverge.
As different gene segments accumulate changes, they can
become very different from one another and the ancestral
gene.
ii. Rearrangement – exons may be rearranged creating new
combinations of coding regions and the potential for new
combinations
iii. Transposable elements
All of these can contribute to new sequence combinations which increase genetic
variation and could potentially benefit the organisms.