Bittel Lectures Flashcards
What characteristics do all living things on the earth have in common?
- all cells store their heredity information in the same linear chemical cod: DNA
- all cells replicate their heredity information by templated polymerization
- all cells translate RNA into protein in the sam way
- each protein is encoded by a specific gene
- all cells function as biochemical factories dealing with the same basic molecular building blocks
- all cells are enclosed in plasma membrane across which nutrients and waste material pass
- life requires free energy
What is short telomere syndrome?
Accelerated aging syndromes often caused by inheritable gene mutations resulting in decreased telomere lengths.
Organs with high cell turnover (bone marrow, liver, lungs, immune system) are commonly affected
What is xeroderma pigmentosum?
cells in most individuals with disease are defective in nucleotide excision repair
sunlight exposure produces pyrimidine dimers in skin cell DNA which can not be repaired
results in abnormal skin pigmentation and acute sensitivity to sunlight
What is Bloom syndrome?
mutation that is usually either nonsense or frameshift mutations in the BLM gene that cause truncation of the BLM protein
What is replication stress?
the slowing or stalling in replication fork progression
What does ionizing radiation do to organisms?
Dislodges electrons in tissue causing free radicals which often damage DNA
What does UV light damage do to organisms?
Induces the formation of pyrimidine dimers: two thymine bases covalently bonded that blocks replication
What does the SOS system in bacteria do?
Allows bacteria cells to bypass the replication block with mutation prone pathway.
If UV light causes formation of a _______ dimer. Then it will ______ replication and _____ the cells unless it is broken. If dimer is repaired, it often leads to _______.
thymine; block; kill; errors (mutations)
What occurs in thymine dimer repair?
(nucleotide excision repair) The dimer is repaired by enzymes that cut out the surrounding nucleotides and fill the space back in.
What is the ATM protein?
member of the phosphatidylinositol 3- kinase family of proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell control
What is the ATM protein?
member of the phosphatidylinositol 3- kinase family of proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell control.
What is the function of the ATM protein?
mobilizing and regulating the cellular response to DNA double stranded breaks function is lost with people who have ataxia-telanglecatasia
What does singling in response to double strand breaks control?
cell cycle checkpoint activation
DNA repair
transcriptional and translation events
apoptosis
How does RecQ helicases protect against cancer?
maintain genomic stability by functioning at the interface between DNA replication and DNA repair
What are the three RecQ family members? What happens if there is a defect in these?
BLM, WRN, RECQ4
defect give rise to cancer predisposition disorders
What is the function of RecQ helicases?
at the interface between DNA replication and recombination to repair damage replication forks
How are BLM and BRCA1 and 2 related?
Part of the same complex
What maintains the 3D structure of RNA?
conventional base pairing
What modifies the 3D structure of RNA?
nonconventional base pairing
What is the RNA sequence the same as?
the non template strand of DNA (coding strand)
What is DNA transcribed by?
RNA polymerase
Function of mRNAs
messenger RNAs, code for proteins
Function of rRNAs
ribosomal RNAs, form the basic structure of the ribosome and catalyze protein synthesis
Function of rRNAs
ribosomal RNAs, form the basic structure of the ribosome and catalyze protein synthesis
Function of tRNAs
Transfer RNAs, central to protein synthesis as adaptors between mRNA and amino acids
function of snRNAs
small nuclear RNAs function in a variety of nuclear processes, inching the splicing of pre mRNA
function of snoRNAs
small nucleolar RNAs
help to process and chemically modify rRNAs and spliceosomal RNAs/ mRNAs
function of miRNAs
microRNAs, regulate gene expression by blocking translation of specific mRNAs and cause their degradation
functions in RNA silencing and post transcriptional regulation of gene expression
function of siRNAs
small interfering RNAs
turn off gene expression by directing the degradation of selective mRNAs and the establishment of compact chromatin structure
function of piRNAs
piwi-interacting RNAs
bind to piwi proteins and protect the germ line from transposable elements
function of lncRNAs
long noncoding RNAs
many serve as scaffolds, they regulate diverse cell processes, including X-chromosome inactivation
What is the TATA box?
25 nucleotides from he transcription initiation site. Protein TBP recognizes and binds to the TATA box providing the initial step to begin transcription.
What removes superhelical tension?
topoisomerase
RNA polymerase is a ______
RNA factory
New mRNA is _____ as soon as it emerges from the polymerase
capped
What are the steps of the 3 enzymes when capping the mRNA?
- Dephosphorylation of 1st nucleotide
- Add a GMP in reverse linkage (5’ to 5’)
- add methyl group to guanosine
* *sometimes another methyl group is added to the ribose on the 1st nucleotide**
What does the cap allow mRNA to do?
be distinguished from noncoding RNAs and important for establishing translation
What does RNA splicing do?
remove intron sequences from newly transcribed pre-mRNAs
What do SR proteins do?
identifiers of exon/intron boundaries
What do hnRNPS do?
help define introns
What percent of mutations cause changes in splice site sequences ?
10%
Why is it important to have a poly A tail?
plays a role in protection and translation
What is an exosome?
protein complex that cleans up damaged RNAs before they leave the nucleus, rich in RNAses and chops up RNA for recycling
What are the steps of transcription?
- RNA polymerase, together with one or more transcription factors, binds to promoter DNA
- RNA polymerase creates a transcription bubble, which operates the two strands of the DNA helix. Done by breaking the hydrogen bonds between complementary DNA nucleotides.
- RNA polymerase adds RNA nucleotides (complementary to the nucleotides on one DNA strand)
- RNa sugar phosphate backbone forms with assurance from RNA polymerase to from an RNA strand
- hydrogen bonds of the RNA-DNA helix break. freeing the newly synthesized RNA strand
- In eukaryotes post transcriptional processing includes polyadenylation, 5’ capping, and splicing
- RNA may remain in the nucleus or exit to the cytoplasm through nuclear pore complex
Do miRNAs regulate protein coding gene expression?
yes
What does miRNA regulate?
embryonic development, cellular proliferation, differentiation, apoptosis
How many diseases are is miRNA involved in?
70 human diseases
Where are rRNAs modified?
in the nucleolus before they leave the nucleus
What does the modification of noncoding RNAs?
snRNP (snoRNAs + specific proteins)
What is the most common modification of noncoding RNAs?
pseudouridylation and 2’O methylation
What is assembled in the nucleolus?
the ribosome and telomerase
What is wobble base pairing?
the nucleotide listed int he 1st column can base pair with any of the nucleotides listed in the 2nd column
Why are tRNA introns spliced out by specialized set of proteins and not splicesomes?
Trimming and splicing require the tRNA to be folded properly and will not proceed if the tRNA is misfolded. Represents a quality control step in tRNA generation.
What are the two steps that aminoacyl-tRNA synthetase hydrolyzes ATP to get energy needed to couple the AA to the tRNA?
- activation of the AA by linking the carboxyl group to AMP
2. transfer the carboxyl group to the hydroxyl group of the sugar at the 3’ end of the tRNA
What 2 adapters ensure the correct amino acid gets incorporated into a peptide?
- aminoacyl-tRNA synthetase which helps ensure that the correct amino acid is coupled to the tRNA
- the tRNA is an adapter whose anticodon pairs with the codon in the mRNA to identify the correct amino acid to adds to the growing peptide
What are the binding sites on the ribosome?
A= amino acyl tRNA P= peptidyl-tRNA site E = Exit
What are the four steps involved in protein synthesis?
- New tRNA binds to A site pairing with codon
- carboxyl end of growing peptide is related from tRNA in P site. Peptide bond formation between the previous AA added and the new one. tRNAs are in P and A site.
- large subunit moves along mRNA held by small subunit, shifting tRNAs to P and E sites on small subunit
- small subunit moves 3 nucleotides alone the mRNA and ejects the tRNA to the E site
Fungi produce many ______ compounds that exploit differences in ______
antibacterial; ribosomal subunit
What can incorrect splicing result in?
premature stop codons
nonsense medicated decay eliminates ______ with premature stop codons
mRNAs
How does the cell know that a protein is incorrectly folded and needs to be discarded?
proteasome searches for misfolded proteins prior to aggregation. Typically the protein has an AA on exterior that shouldn’t be there.
What are the functional domains of the proteasome?
- ubiquitin receptor
- unfoldase
- ubiquitin hydrolase
How does the body know to make different cells even if they all came from basically the same one?
Different signals with determine what cell to be made
