IR WEEK 2 Flashcards
what is the spontaneous loss of ~500 purine (A,G) bases lost per cell per day because of hydrolysis of the glycosal linkage to deoxyribose
depurination
when does depurination occur?
when the bond connecting a purine to its deoxyribose sugar is broken by a molecule of water (hydrolysis) resulting in a purine free nucleotide that can’t act as a template during DNA replication (results in a deletion)
what is the spontaneous removal of the amine (NH2) group from ~100 cytosines per cell per day to form uracil
deamination
when does deamination occur?
when hydrolysis wipes away the NH2 from cytosine and replaces it with an oxygen to form uracil and an ammonium ion (results in a substitution
List the spontaneous DNA mutations that require DNA repair
- depurination
- deamination
- spontaneous oxidative destruction
- uncontrolled methylation
- hydrolytic attack
reactive oxygen radical or chemical exposure causes base damage
spontaneous oxidative destruction
forms pyrimidine dimers via covalent linkage between 2 bases
UV damage
DNA glycosylases are specific for altered DNA bases. it is detected by the glycosylase enzyme “flipping out” each nucleotide so it can be checked by the endonuclease and repaired if necessary
base excision repair
recognition of dimer begins with this repair
delete
BRCA1
breast and ovarian cancer; repair by homologous recombination is affected
Ataxia Telangiectasia (AT)
leukemia, lymphoma, gamma ray sensitivity, genome instability; ATM protein is affected
cockayne syndrome
UV sensitivity, developmental abnormalities; coupling of nucleotide excision repair to transcription process is affected
xeoderma pigmentosum
skin cancer, UV sensitivity, neurological abnormalities; nucleotide excision repair is affected
DNA is transcribed into RNA
transcription
a sequence of DNA nucleotides that signal the starting point for RNA synthesis
promoter
comparing many sequences with the same basic function and tallying up the most common nucleotides found at each position. it serves as a summary or “average” of a large number of individual nucleotide sequences
consensus nucleotide sequences
genes carried in a cells DNA, specify the amino acid sequence of proteins, and the RNAs that are copied from these genes (which ultimately direct the synthesis of proteins)
mRNAs
do not code for a protein
non coding RNAs
will form to compensate for each 10 nucleotide pairs that are open (unwound). the formation of this is energetically favorable because it restores a normal helical twist to the base paired regions that remain
DNA supercoiling
state the central dogma
dna to mrna to protein
transcribes the genes 5.8S, 18S, 28S rRNA genes
RNA Polymerase I
transcribed all protein coding genes, plus snoRNA genes, miRNA genes, siRNA genes, incRNA genes and most snRNA genes
RNA Polymerase II
transcribes tRNA genes, 5S rRNA genes, some snRNA genes and genes for other small RNAs
RNA Polymerase III
function in a variety of nuclear processes, including the splicing of pre-mRNA
snRNA (small nuclear RNA)
help to process and chemically modify rRNAs
snoRNA (small nucleolar RNA)
regulate gene expression by blocking translation of specific mRNAs and causing their degredation
miRNA (micro RNAs)
a transcribed segment of DNA; information in just one gene for just one RNA molecule or single protein (or group of mRNAs if there is splicing)
transcription unit
a sequence of DNA Ts and As located ~30 nucleotides upstream from the transcription start site.
TATA box
form the basic structure of the ribosome and catalyze protein synthesis
rRNA
joins together different portions of an RNA transcript to eliminate the intron sequences; also provides eukaryotes with the ability to synthesize several related but different proteins from the same gene
RNA splicing
allows activator proteins to communicate properly with the RNA polymerase II and with the general transcription factors
mediator
the large assembly of RNA and protein molecules that performs pre-mRNA splicing in the cell, snRPs form the core
spliceosomes
the nucleotide sequence of a gene, through intermediary of mRNA, is instead translated into the amino acid sequence of a protein by rules
genetic code
each group of three consecutive nucleotides in mRNA is called (this) and each (this) specifies either one amino acid or a stop to the translation process
codon
allows an RNA sequence to be translated in anyone of 3 different frames
reading frame
a set of three consecutive nucleotides that pairs with the complementary codon in an mRNA molecule
anticodon
mismatch at the third position, can base pair with any nucleotide listed in the shown column; explains why so many of the alternative codons for an amino acid differ only in their third nucleotide
wobble
a complex catalytic machine made from more than 50 proteins and several RNA molecules
ribsomes
RNA molecules that posses catalytic activity
ribozymes
small set of RNA molecules that allow the binding to both the codon and the amino acid
tRNAs
sugar group is ribose, uracil replaces thymine (loses methyl group), sometimes there are unique base pairings G wit U
RNA
how does tRNA become attached to the appropriate amino acid?
tRNA requires aminoacyl-tRNA synthetase for recognition and attachment of the correct amino acid to the 3’ end
what direction are proteins synthesized in
N-terminal end to C-terminal end
this ribosomal subunit is important for matching tRNA to codon on mRNA
small subunit
this ribosomal subunit catalyzes the formation of peptide bonds between amino acids
large subunit
Four major steps to chain elongation
tRNA binding
peptide bond formation
large subunit translocation
small subunit translocation
what speeds up eukaryotic translation process?
elongation factors EF1 and EF2
how is codon-anticodon match checked?
small rRNA subunit forms hydrogen bonds between codon and anticodon; if match is correct, GTP hydrolysis occurs which moves the translation process along
what does the mRNA 5’ cap do?
marker to cell that this is an mRNA
essential for translation
binds a protein complex as a recognition factor: cap binding complex
this is considered a molecular mimic, similar in 3D conformation to tRNA which helps it bind to the A site
release factor
allows more than one protein to be synthesized from a single mRNA by changing reading frame by ignoring a start or stop codon
translational frameshifting
21st amino acid can be inserted directly into a growing polypeptide using
translation recoding
produced from serine tRNA that is enzymatically altered, binds to stop codon
selenocysteine
misplaced STOP codon
nonsense mediated mRNA Decay
a collection of rare disorders involving impaired ribosome biogenesis and function; mutations affect translation and protein synthesis
ribosomopathies
caused by truncated protein bc STOP codon is misplaced (Nonsense mutations)
CF mutations
Duchennes MD
betathalassemia
hurlers syndrome
Disorders of missense mutation
sickle cell
certain types of CF mutations
certain cancers
Have specific functions in altering a misfolded protein hsp60 and hsp70 are examples
chaperones
initiates early protein folding; looks for stretches of hydrophobic amino acids which trigger ATP hydrolysis
HSP70
aids in helping incorrectly or incompletely unfolded proteins fold completely
HSP60
contains proteases for digestion of proteins
proteasomes
serve as a recognition marker for proteasomes when it is bound to misfolded proteins
ubiquitin
histone regulation
monoubiquiliation
endocytosis
multiubiquitylation
proteasomal degradation and DNA repair
polyubiquitylation
surface amino acid sequences recognized by a set of enzymes
degrons
brain/spinal cord are sensitive to protein aggregates. protein aggregates can cause
alzheimers
huntingtions
ALS
parkinsons
RNA polymerase is part of the repair process by stalling at DNA alterations (specifically NER) during transcription and calls fourth coupling proteins which direct excision repair machinery to these sites
transcription-coupled repair
this syndrome is caused by a defect in transcription coupled repair
cockayne syndrome
methods for repairing double stranded DNA breaks
non-homologous end joining and homologous recombination
involves removing a set of nucleotides, then ligating the strands back together
non-homologous end joining
occurs after replication (S and G2 phases) when nearby daughter DNA duplex and serve
as template for repair
homologous recombination
group of enzymes that form phosphodiester bonds between ribonulceotides
RNA polymerases
unwinds DNA at the transcription start point, phosphorylates Ser5 of the RNA polymerase CTD; releases RNA polymerase from the promoter
TFIIH
RNA polymerase I transcribes……
rRNAs
