Mutation and Gene Regulation Flashcards
point mutation
one nucleotide is replaced with another
missense mutation
One amino acid substituted for another
nonsense mutation
premature stop codon
Frameshift mutation
all/most amino acids changed
eliminate one letter, all the codons will shift
silent mutation
o No change to function
how do we get mutations
• Most spontaneously arise during DNA replication
o Can be detected and deleted by DNA repair enzymes (polymerase and others)
o Some slip by
• Other mutations can be induced by exposure to mutagens,
mutagens
a substance that causes mutations
Radiation induced mutations
- UV rays
- X rays
- Nuclear power plants
chemical induced mutations
- Exhaust
- Chemicals in cigarette smoke
- Chemicals in plastics
loss-of-function mutations
o Something you could before, but can’t do now
• Missense and frameshift
• Gene is nor expressed
• Gene no longer codes for a functional protein
gain of function mutations
o Now do something you didn’t do before or of more of something than you did before
o Mutation in cell cycle control gene now results in more cell division
o Replication of genes on the chromosome leads to greater expression
chromosomal mutations
• Large chunks of DNA can be duplicated/moved/mutated/deleted, etc when changes come to the chromosomes themselves
o Chunks of DNA from one chromosome might move to another chromosome
genetic regulation
- Almost every cell in your body has your complete genome
- Not all genes are needed all the time in every cell
- Organize compress regulate
Cell differentiation
o The process by which cells become specialized for their role in the body
o We start with stem cells, which can become any cell type
o Cells progressively become more and more specialized, until they are well suited to one or a few tasks, but unable to perform others
Differentiation
- Starts with a pluripotent stem cell
- During cytokinesis, not all the same cytoplasmic components will end up in each daughter cell
- As the cells divide, different transcriptional programs are turned on via signals from the environment
- Each division is asymmetric: produces one cell that retains its undifferentiated capacity as a stem cell
- The other cell from each cell division acquires new traits through the transcription of genes
mechanisms for gene regulation
- Control over RNA polymerase and the initiation of transcription
- Stretches of non-coding DNA that promote or suppress transcription of genes
- Alternations in the structure of chromatin near the gene to make it easier/harder for the transcription enzymes to access the gene
transcription factors
o Proteins that recruits RNA polymerase to the promoter sequence of particular genes
o Are often under control of cell signaling cascades
histones
- Histones are sticky proteins and are attracted to each other
- Histone attraction can hide the DNA, making it inaccessible for transcription
- Adding acetyl groups to the histones reduces their attraction to each other, spreading out the DNA and making it available for transcription
- Reversible
makes genes more accessible to transcription factors
DNA methylation
add methyl groups to the nucleotides themselves, preventing access by DNA polymerase
• DNA methylation is relatively permanent once methylated (even during embryonic development) genes stay that way for life
• DNA methylation is necessary: mutation of methylating enzymes leads to developmental abnormalities
other facts about methylation
- Cells pass on methylation to daughter cells
- As a cell differentiates it gains methylation
- New research is able to dedifferentiate skin cells into stem cells buy de-methylation of DNA and addition of other factors
alternative splicing
different protein products can be achieved from the same transcript by altering which exons are spliced out
very popular with viruses
• RNA processing and breakdown
o Cap and tail length can determine how long a transcript will remain in the cytoplasm, and therefore how much protein will be made
initiation of translation
o Cell may make functional RNA but delay the start of translation until conditions are optimal
o Ex: RBCs will not initiate translation unless there is sufficient iron in the cell
microRNAs
miRNAs) are partially complementary to mRNAs and inhibit their translation
• low affinity attraction with the mRNA
• will bind temporarily to start inhibition
• will eventually fall off so transcription can continue
• mRNA: UAGCCAGUAC
• siRNA: AUCGCUCAUG
short interfering RNAs
- are exactly complementary to mRNAs and cause them to be degraded
- high affinity with mRNA so it will bind for a looong time
- single strand of mRNA will not be translated
- single-double stranded molecule=translation can’t happen
preventing translation
• regulatory proteins can tempo. Block until conditions are optimal
protein activation
• some proteins are made in an inactive form, and then are activated under the right conditions
insulin is made in an inactive form, a separate enzyme cleaves it and activates it
epigenetic and disease
o Epigenetics appear to play a role in the development of cancer by turning on/off genes that control cell replication
o May play a role in development of type II diabetes (methylation or de-methylation of genes involved in regulating metabolism)
o As we age, we progressively de-methylate our genome. May be linked to increase in cancer
