Biology 1002B Study Guide - Final Guide: Tumor Suppressor Gene, Natty, Synonymous Substitution

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Published on 20 Apr 2013
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Biology 1002 Natty Liu
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Final Exam Outcomes
Lecture 18: Cancer
Four most common types of cancer in Canada
Breast, prostate, lung, colorectal
Leading cause of premature death in Canada, 25% of Canadians can expect to die of
cancer
Likely factors contributing to cancer incidence in Canada
Men are at higher risk for cancer than women
Rates among youth are rising
Role of cyclin/CDK complexes in cell cycle regulation
Cyclin / CDKinase complexes regulate cycling
G1S checkpoint prevents cell from replicating it‟s DNA if it‟s damaged until everything is
repaired which is monitored by CDK (cyclin-dependent kinase)
Cyclin production cycles are with cell cycle produced early on and binds & activates
CDK
CDK complex then phosphorylates whole bunch of targets downstream, releasing the
G1S checkpoint
Example of post-translational regulation of protein function
Role of proto-oncogenes, tumor suppressor genes and oncomirs in cancer
Oncogenes “cancer genes” aren‟t actually cancer genes but really embryo genes
Normal genes become an oncogene due to mutations or deregulation
Expression of proto-oncogenes promotes cell cycling: Epidermal growth factor receptor
(needed for rapid cell division, if they are over expressed they can promote tumor
growth)
Expression of tumor suppressor genes slow cell cycling: p53
“TP53” is a master tumor suppressor gene, coding a transcription factor whose activity
can result in: increased DNA repair, cell cycle arrest by blocking cyclin / CDK, apoptosis
Did not evolve to shut down tumor, evolved to shut down cell division
Prevent cell division, if they become mutated then we get more out of control division
Inappropriate expression of miRNA can promote cycling: oncomirs
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Micro RNAs turn out to be very integral in cell division / regulation
HeatMap shows miRNA overexpressed (red) / underexpressed (blue)
In tumors have lots of blue, each tumor has its own fingerprint of miRNA expression
Role of p53 gene
Tumor suppressor gene, transcription factor (regulates activity of other genes)
Normal functions to shut down cell division when a cell is stressed
When DNA is damaged, p53 activates genes that stop cell growth / trigger death
Mutation to this gene can cause tumors
Explanation for why increased cancer risk can be inherited
Cancer can run in families, related people are at higher risk sometimes
Sporadic cancer requires new loss of function mutations in both alleles
BRCA1 puts breaks on cell division, but mutation in both those alleles and now you have
lost the tumor suppressor activity and the cells divide out of control
Familial cancer requires loss of function mutations in one allele
Much higher risk if you inherited one mutation from parent (need 1 instead of 2 in order
to develop a tumor)
Explanation for why cancer incidence tends to increase with age
Cancer is progressive, accumulated more mutations when you‟re older
Most cancers require several mutations to occur before you get a tumor
Accumulated deregulation gives rise to a tumor
Death rates are high because there‟s more old people (problem in aging populations)
Role of stem cells in tumor growth
Cancer may begin as alterations to gene expression in stem cells
Pluri potent stem cells are able to differentiate into a wide range of tissue types (know
how to be different types of cells)
One is the stem cell, one becomes progenitor that differentiate into what is needed
Stem cells, progenitors and differentiated can all suffer mutations and become cancer
stem cells
Tumors may be driven by cancer stem cells, cells are not the same in tumors
Evidence that epigenetic regulation may be relevant in cancer
Some tumor cell nuclei can be re-programmed
Tumors have mutations but maybe they don‟t start with mutations but epigenetic
changes that are potentially reversible
Experiment: mice at high risk for brain cancer inheriting one defective tumor suppressor
and suffer another mutation that can give risk to tumor (dividing out of control due to loss
of tumor suppressor gene)
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Mouse egg cell take nucleus out of the cell and replaced with nucleus from the tumor
cell and “fertilize”…tumor makes a mouse not a tumor
When you put the tumor in the environment of an egg, it reprograms and is normal
How does HPV cause cervical cancer?
HPV is a DNA virus infects the cells on the cervix
Lecture 19: Molecular Homology
Strategies for determining if features are homologous
Homology means common ancestry, does not mean similar
Comparative Genomics: genome sequences of different species are compared
Sequence genomes genome annotation protein prediction align sequences
determine homology
Sequences detected by annotation programs to detect open reading frames (ORF)
Use of computer algorithms to detect: promoter elements, intron / exon boundaries,
other conserved DNA motifs
Need to determine the longest open reading frame from start to stop (largest number of
amino acids)
Six possible reading frames from the predicted protein-coding sequence
Characteristics that are, and are not, common between homologous genes
Look for similar sequences in a database NCBI Genbank
Arrange sequences to show regions of similarity
From sequence similarity one can infer structural and functional similarity as well as
evolutionary relatedness
Usefulness of BLAST analysis of sequences in Genbank at NCBI
BLAST Basic local alignment search tool, much faster just looks for regions of very
high similarity, doesn‟t try to force two sequences together
CLUSTAL Global algorithm that starts at the beginning of the protein coding sequence
and tries to arrange similar bases (introduce gap if they don‟t)
Reasons why amino acid sequence comparisons are more informative than nucleotide
sequence comparisons
More information in an amino acid sequence of same length
The genetic code is redundant, amino acids are much more reserved
DNA databases are much larger, protein database only have translated sequence that
codes for a protein predicted, much more curated (specific & refined)
Mathematical relationship among total information, # of symbols, # letters in the alphabet
How many bits of information in each letter of a four-letter alphabet?
A 00 G 01 C 10 T 11
I is the total information in a message with G symbols written in an “alphabet” of n letters
I = G lnn / ln2
Relative number of bits of information in a single nucleotide vs. single amino acid
A string of 20 amino acid has much more information 20 nucleotides
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Document Summary

Four most common types of cancer in canada: breast, prostate, lung, colorectal, leading cause of premature death in canada, 25% of canadians can expect to die of cancer. Likely factors contributing to cancer incidence in canada: men are at higher risk for cancer than women, rates among youth are rising. Role of cyclin/cdk complexes in cell cycle regulation. G1s checkpoint prevents cell from replicating it s dna if it s damaged until everything is repaired which is monitored by cdk (cyclin-dependent kinase) Cyclin production cycles are with cell cycle produced early on and binds & activates. Cdk complex then phosphorylates whole bunch of targets downstream, releasing the. Example of post-translational regulation of protein function. Inappropriate expression of mirna can promote cycling: oncomirs. Biology 1002 natty liu: micro rnas turn out to be very integral in cell division / regulation, heatmap shows mirna overexpressed (red) / underexpressed (blue)

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