BIOL 3000 Genetics - Auburn Dr. S - Exam 4

Simultaneously

When does prokaryotic Transcription, translation and protein formation occur?

Transcription stops

What happens when the protein is no longer needed in prokaryotic cell?

Prokaryotic gene expression

Regulation of Transcription is the primary method of controlling gene expression

Prokaryotic Organisms

single cell organisms lacking a defined nucleus.

Proteins that regulate chromatin remodeling

ATP‐Dependent Chromatin Remodeling Complexes and Histone Modifying Complexes

ATP‐Dependent Chromatin Remodeling Complexes

use energy from ATP to loosen chromatin (Protein complexes that regulate expression by moving, ejecting or restructuring nucleosomes. Once protein complex binds to DNA around the nucleosome, chromatin structure is loosened allowing movement of the histone core octamer)

Histone Acetylation

Expression

Histone De‐Acetylation

Silencing

DNA Methylation

Silencing

DNA De‐Methylation

Expression

Transcriptional Regulation

Signaling Control of Gene Expression

Proteins

What are transcription factors?

Factors for gene expression

initiating signal, signaling pathway cascade, activation of transcription factor, recruit transcription complex and RNA poly II, initiated at promoter site

Anywhere

Mutations of the transcriptional regulations can happen _____ along the pathway

Early

When would the cell stop a process so it doesn't use energy?

Hormone (gene expression)

molecule that is produced in one cellular location but whose effects are seen in another

RECEPTORS

HORMONES (gene regulation) require the target cell to have ______ specific for that hormone if there will be a resonance.

helping or hindering

Transcription Factors control the rate of gene transcription either by __________ RNA Polymerase binding to DNA

Transcription Complex

Transcription factors interact with other proteins to build a ________ that may increase transcription as much as 100‐fold.

Transcription Factors

__________ bind to specific DNA sites or regions either alone or in concert to affect transcriptional rates of specific genes.

cis‐ activating factors

binds to DNA itself

trans‐ activating factors

binds things that act on the DNA

Promoter

region of DNA located upstream but near the transcription start site of a particular gene that initiates transcription.

Enhancer

region of DNA that binds to ACTIVATOR PROTEINS to activate the transcription process.

TATA Box

DNA sequence found in the promoter region where Transcription Factor Complex proteins bind, specifically TATA Binding Protein.

Silencer

region of DNA that binds to REPRESSOR PROTEINS to prevent binding of RNA Pol II to the promoter.

Insulator

region of DNA that blocks the interaction of enhancers with promoters.

PROMOTER (Core Promoter)

site of TATA‐binding protein and Basal Factor binding; responsible for BASAL LEVEL OF EXPRESSION; Binding by GENERAL TRANSCRIPTION FACTORS.

PROMOTER‐PROXIMAL ELEMENTS

site of additional ACTIVATOR PROTEIN binding; responsible for INDUCED/REPRESSED LEVEL OF EXPRESSION; Binding by TISSUE SPECIFIC TRANSCRIPTION FACTORS

How promoter-proximal elements occur

Looping of DNA brings transcription factors and trans‐activating factors together. Leads to higher efficiency transcription of gene of interest.

Insulators

prevent transcription of Non‐Target Genes

Messenger Ribonucleao‐proteins (mRNPs)

Export of mature mRNA from the nucleus to the cytoplasm is controlled by a large number of ______________. mRNA export is through large multi‐protein pore Complexes

Mature microRNA (miRNA)

a class of naturally occurring, small non‐coding RNA molecules whose main function is to down regulate gene expression (made in nucleus, form hairpin, go to cytoplasm)

Biomarkers

Deregulated in different types of cancers making them highly useful as __________ in future diagnostics as well as attractive drug intervention targets

Dicer

removes the hairpin loop region leaving dsRNA in miRNA regulation

miRNA‐protein complex

Blocks Translation by the ribosome and speeds up deadenylation (breakdown of Poly‐A Tail)

Not making protein

5' cap not there or start codon mutated, or reading frame offset (making a protein but not the right one)

Ribosomal Pausing

stacking of ribosomes on an mRNA molecule caused by changes in cellular environment. Can result in release of the ribosome and premature degradation of the incomplete polypeptide

elongation factors

If _______ are mutated then we change the protein.

Structural post-translational regulation

breaking disulfide bonds and proteolytic cleavage (ex. insulin)

Functional post-translational regulation

myristoylation and phosphorylation

Regulation of Gene Expression

includes a wide range of mechanisms used by the cell to increase or decrease the production of specific genes.

Up‐Regulation

process which results in INCREASED expression of one or more genes

Down‐Regulation

process which results in DECREASED gene and corresponding protein expression

Genetic Material "MUST HAVES"

Effective TRANSFER between generations, Ability to store VAST AMOUNTS OF INFORMATION, Information can be changed / MUTABLE, Effective REPLICATION / HIGH FIDELITY

Substitutions

transition mutant and transversion mutant

Insertion/deletion

frameshift mutants and in-frame mutants

Functional mutants

gain/loss of functional mutants and lethal mutants

Transition mutant

exchange a purine for a purine or a pyrimidine for a pyrimidine (A to G/C to T)

Transversion mutant

exchange nucleotides outside of nucleotide family; exchange a purine for a pyrimidine

Transitions

Do transitions or transversions happen more often?

Keep the same structure

Why are transitions more common from transversion?

Silent, missense, nonsense

types of insertions/deletions

Silent mutation

changing one codon to a synonymous codon causing no change in the amino acid sequence of the protein

third position wobble

How can silent mutations not be expressed in phenotype?

Missense mutation

changing one codon to a different codon resulting in a change in the amino acid sequence of the protein

Sickle cell anemia

Example of missense mutation from glutamine to valine and changes shape of red blood cells?

Nonsense mutation

changing one codon to a "STOP" codon resulting in premature stoppage of translation (very severe)

Cystic Fibrosis (CF)

approximately 10% of all CF cases worldwide is caused by a nonsense mutation in the CFTR protein resulting in nmCF.

Duchenne Muscular Dystrophy (DMD)

approximately 15% of DMD cases are the result of the absence or very low levels of the dystrophin protein caused by a premature STOP codon

Frameshift mutation

gain or loss of a nucleotide (or nucleotides) that result in change in the reading frame of the codon (still has the polypeptide chain but it is gargled)

Crohn's Disease

a form of inflammatory bowel disease. Symptoms include abdominal pain, fever and weight loss. Affects 0.3% of people in Europe and North America (insertion - changes reading frame)

In-frame mutation

gain or loss of a nucleotide or trinucleotide set that does not change the reading frame of the codon

Loss‐of‐Function Mutation

results in a gene product with little or no functionality (Amorphic: complete loss of gene function). Most of the time, these phenotypes are Recessive.

Recessive

Loss‐of‐Function Mutation dominant or recessive?

Amorphic

complete loss of gene function

Gain‐of‐Function Mutation

results in a gene product that has gained a new and abnormal function (Neomorphic: a new or different function from normal).

Dominant

Gain‐of‐Function Mutation dominant or recessive?

Neomorphic

a new or different function from normal

Lethal Mutation

mutation that leads to the death of the organism carrying the mutation.

Somatic Cells

non‐sex cells range from mild to severe not passed to next generation

Germ Cells

sex cells / gametes typically more severe manifestation passed along to offspring

Spontaneous mutations

any mutation where no artificial factor or external regulator causes the mutation

Spontaneous

replication errors and chemical changes

Induced

environmental factors and chemical interactions

Wobble

non‐complimentary bases can pair due to the flexibility of DNA double helix which can accommodate slightly misshaped pairings. (non-watson and crick base pairing)

Slipped Strand Mis‐pairing

involves denaturation and displacement of DNA strands that results in mispairing of complimentary bases

Chemical Changes

mutations caused by normal chemical reactions that occur in the cell.

Depurination

a chemical reaction in which a beta‐N‐glycosidic bond is cleaved by hydrolysis causing the release of an Adenine or Guanine from a DNA strand.

Deamination

the hydrolytic removal of an amine group from a nucleotide releasing ammonia and converting the nucleotide to another molecule.

Apurinic site

still has backbone but lost a base. Any base can add itself (results in mutation)

Free Radicals

very unstable and quick reacting molecule that "steals" electrons from nearby stable molecules

UV Light

causes pyrimidine dimers by the formation of covalent linkages localized on cysteine double bonds (covalent bond that created a bump on DNA sequence)

Antioxidants

a substance that inhibits oxidation, especially one used to counteract the deterioration of stored food products.

Natural antioxidants

uric acid, vitamin C, vitamin E

Free radical causes

UV light, air pollutions, smoking, radiation

Mutations

What can chromosomal rearrangements be considered as?

Ectopic recombination

breakage of chromosome in meiosis

Chromosomal mutations

chromosome duplication and deletion

Larger

The ______ the chromosome duplication or deletion the _______ they affect the chromosome

Small deletions effect

less likely to be deleterious

Large deletions effect

often fatal

Medium deletions effect

responsible for a number of genetic diseases.

transposable elements (TEs)

Sequences of DNA that move (or jump) from one location in the genome to another.

Jumping genes

What are transposable elements also known as?

Transposable elements (TEs)

Thought of as junk DNA and makes up 40% of the human genome (regulatory function)

Jumping genes (transposable elements)

Barbara McClintock and corn to discover?

reverse transcriptase

What do CLASS 1 TEs require to transpose?

Transcription of RNA into DNA

What is the process by which CLASS 1 TEs transpose?

RETROTRANSPOSONS

What type of transposons are CLASS 1 TEs?