Lecture 7 - special topic Dieases assoc w/ defects in DNA RRR Flashcards
What is the main enzyme that replicates DNA and what direction is it done in?
DNA polymerase and 5’ to 3’.
What is formed as a consequence of DNA poly moving 5’ -> 3’?
leading and lagging strands
What processes are the result of DNA’s high fidelity in complex organisms?
5’->3’ polymerization
3’ -> 5’ exonuclease
Strand-directed mismatch repair
If we had perfect replication occur what would be the result?
CONCEPT
No variation in DNA. No specialized cells.
How is DNA replication initiated ?
- Pre-replication complexes bind to origin of replication
- activated helicases find ORI (plus cd6K)
- DNA poly and other proteins added.
- Phosphorlaytion initates DNA synthesis at the right time
What structure is formed by telomeres repeats?
The T loop is formed by the insertion of the the single 3’ overhang into the duplex
What is the function of telomerase
- To maintain and prevent degeneration of the length of the G-T rich telomere region
- allow DNA replication to finish by placing final RNA primer,
- PS: formed in nucleolous
What is the short telemere syndrome?
STs result from acceleration aging syndromes
They are caused by inheritable diease mutations resulting in decreased telomere lengths
Autosomal recessive
Organs high cell turnover are affected like bone marrow, liver, and immune system.
Telomerase is a protein used to maintain the ends of the cell and helps avoid senesensce, a mutation resulting in the total siliencing of telemerase’s function would result in what?
Concept
it would result in rapid degeneration of the chromsomes. telerases help indicate a cell mitotic lifespan. A total distruprtion of telormease function would rarly be seen because it would result in death of the cell.
Cancer is indicated by a _______ .
Concept
Genomic instability
it only takes one cell too avoid all cell check points. Once this occurs it is able to conduct angiogensis and uncrontrolled cellular replciation.
In a broad sense, translesion DNA polymerases are used to repair DNA in emergencies and in very damaged areas. Unexpectedly, they also result in what?
Increased or great potental for adaptation, natural selection , or mutation (any of these work).
Slide def: allow polymerasese to skip over distorsions/dimers but often result in mutations
This because they add what ever dNTP to the DNA b/c most of the DNA is introns. however on the small chance that it repairs an “exonic” region this could be expressed in deleterious or benifical manner.
What must occur b/w homologous chromosomes to allow meiosis to proceed?
Double strands breaks (also must be repaired)
(this is also another way to increase natural selection but contributes to our DNA prone”ness” to breaks )
What are the two types of double strand breaks and how do they differ?
- Non homologous end joing
- Breaks are re-join to a chromosome wether its homologous or not
- Homologus recombination
- requires invasion via a 3’ strand of a homologous chromosome to repair and can result in cross over or gene conversion
What delays progression of the cell cycle ?
DNA damage
What factors potentially causes mutations ?
- Spontaneous replication errors
- Spontaneous chemical changes
- Chemically induced mutations
- Radiation
stressful situations can induce what?
CONCEPT
an increase risk of mutations
What is a result of Oxidative stress and whats a one example of it?
free radicals which causes a guanine to transform dihydrodeoxyguanine (which is not important) and cause it to mispair with adenine
A source of is ionizing radiation which dislodges eletrions in tissues cause free radicals
what is the most common form of radiation that causes mutations ?
UV light induced pyrmidine dimer
the formation of pyrmidine dimers like (T-T) or (C-T) from UV light. These dimers block replication with a muation prone pathway.
Common source of skin cancer (melanoma)
What repair is responsible for a pyrimidine dimer repair?
NER
How is xeroderma pigmentosum transferred?
gentically, and its autosomal recessive.
What is the underlying mechanism for Xeroderma Pigmentosum and how does it results in its symptoms?
- The combination of sunlight exposure and abnormal skin pigmentationa + sensitivity produces pyrimindine dymers in skin cell DNA which cannot be repaired.
- Keep in mind, The cells in infected indivduals are DEFECTIVE in nucleotide-exicsion repair.
- Strong predisposition to cancer b/c mutations persist
What type of repair is essential for prevention of skin cancer development?
NER
- What does ATM protein do?
- A kinase
- Generates intracellular signals that alert the cell to DNA damage (specifically DS breaks) and upregulate expression of DNA repair genes
What is Ataxia Telengiectasia? (underlying Mechanism and how do mutations results in symptoms )
- Mutations in ATM and assocatied with Neurodegeneration, cancer chance increase, genome instability,
- Because a defective ATM allow mutations to grow and divide uncontrollably.
- they also die in cells wierdly and affecting parts of the brain involved in coordianting movement
- AUTOSOMAL RECESSIVE OF THE ATM GENE
What are the symptons of Ataxia telangiectasia?
Porgressive cerebellar dysfunction b/w 3 and 4 years old manifest as
Gait and truncal ataxia
head tilting
slurred speech
oculomotor apraxia and abnormal ocular saccades
immunodeficiency
True or False: Carriers of AT , who are not expressing the diease, are more susceptable to developing caner.
True.
Fun fact: about 1 percent of the US pop carry 1 mutated copy
what type the mutations occur in BLM and result in bloom syndrome ?
Nonsense or framshift mutations
or
Stop codons or deletons
What is Bloom Syndrome?
Results from a muation in the BLM gene and is an auto reccessive disorder
What are us the basic clinincaly side of the bloom syndrome?
Causes proportional dwarfism
male indertility and female subfertility
Sun induced erthemia of the face “butter fly”
type 2 diabeties
Narrow face and prominant ears
What componets make up Rec Q helicase
BLM, WRM, and RECQ 4 and are assocated with a predisoposition for cancer
WHat is the function of Rec Q?
Its propsed function is as an interface b/w DNa replication and recombination to repair damaged DNA replication forks
“Care taker tummor repressor”
Maintains genomic stability
highly conserved
- Ex: seen in Ecoli maintaining the same processes
How are BLM and BRCA1 and BRCA2 related?
Form the BASC complex.
Form a survalence complex for mutation or DNA damage
Mutations = a rise genomic stability = rise in cancer
Trigger apoptosis to fix
activated via ATM
What is a spliceosome?
splices mRNA
alternate splicing
made up of snRNAs
What does this picture signifiy?
central dogma
flow of DNA to RNA to Protein occurs in all living cells
What are two qualities of interspersed DNA ? (verbal)
REgulatory
tolerant of DNA mutations
“not much know buts it not just junk”
Why might RNA molecules be considered as the first molecule to store the information necessary to propagate life?
B.c DNA is NOT enzymatically active and RNA IS!
this basically means that RNA can FOLD on itself to for 3D structures (stillmaintaing its Base Pairing) w/o the aid of proteins
The RNA sequence is the same as ____________?
non template strand of DNA
What carries out trancritpion of DNA and how does it supply its energy?
RNA polymerase II , breaking rNTP’s triphosphate bonds
How far away is the tata box from initation site?
25 nucleotides away
True or false the promoter can only be on one strand
FALSE
it can be on either strand
What does……?
RNA Polymease I
RNA polymerase II
RNA polymerase III
do
RNA polymerase I - code rRNA genes (5.8, 18, 28)
RNA polymerase II - main transcription protein for protein coding and non coding rregions
RNA poly III = tRNA and some rRNA
WHat binds and recongizes the tata box
TBP and begins inital step trancription
What are the set of general transcription factors that RNA poly II needs?
BRE, TATA, INR, and DPE
must be conserve for transcription activity but doesnt aid in precise activity
what are the clincally symptons of ST
Premature graying of hair, unexplained cytopenias (low blood cell count), idiopulmanry fibrousis, cryptogenic cirrhosis
