Final Study Guide Flashcards
what are the 5 points of control?
chromatin stage
transcriptional stage
translational stage
post-transitional control into cytoplasm (regulation of RNA transport)
what does the chromatin stage involve?
regulation at the chromatin stage can occur through a variety of mechanisms
including CpG islands and histone modification
what are CpG islands? what does methylation of cytidine cause?
target sites of methylation are cytidine residues
areas rich w/CpG are known as CpG islands
methylation of cytidine down-regulates transcription
what is histone modification? what does methylation vs acetylation do?
methylation or demethylation of lysine and arginine
methylation = down-regulation of transcription
acetylation = up-regulation of transcription
how can histone be modified?
ubiquination
sumoylation
phosphorylation
why is the chromatin stage important in relation to CA?
b/c potential therapeutic for CA are often designed to demethylate or deacetylate depending on the needed end result
what is involved in the transcriptional stage?
copies genes, splits strands, mRNA shuttled out to nucleus to cytoplasm
promoters cause conformation changes and are seen in all coding genes
what do promoters start? examples? located where?
signal for DNA production
ex: TATA, CCATT boxes
located upstream of transcription site
what is involved in the translational stage?
RNA processing - addition of 5’ cap and 3’ poly (A) tail; removal of introns; splicing of exons
cap/tail communication - communication btw 5’ and 3’ ends of mRNA leading to enhanced translation
what is in the post-translational control into the cytoplasm?
only some RNA fxns w/in nucleus so rest needs to get out so proteins can be made
leaves nucleus via nuclear pores
able to leave through pore by caps being added to the ends of the mRNA which causes a shape change
what are the proteins involved in moving mRNA to the cytoplasm? what is required for entry vs exit?
NPCs (nuclear pore complexes)
karyopherins
Ran (Ra-s related nuclear protein)
small molecules can enter nucleus w/o regulation but macros like RNA and proteins require associated with karyopherins called importins to enter the nucleus and exportins to exit
what is in post-translational modification? how can proteins be modified?
protein biosynthesis
ribosomes translate mRNA
ribosomes translate mRNA into polypeptide chains
protein modified by folding, cutting or other processes like adding functional groups or phosphorylation
what are the 5 genetic dzs to know for boards?
klinefelter syndrome (47XXY) turner syndrome (45X, 46XX, 47XXX) alien 3 syndrome - 47XYY fragile X huntington dz
what is klinefelter’s syndrome? genetic makeup? also known as? error where? what is likely to occur to sex organs?
47XXY
aka hermaphrodite d/o
sex chromosome aneuploidy
error in meiosis 1 - non-disjunction of X chromosomes
presence of both sex organs VERY rare
hypogonadism more likely dt dec T and incr LH, FSH
ssxs of klinefelters? associated RFs and diseases?
appears over time, not at birth
physical traits become more evident during puberty dt lower T levels - less muscular body, less facial and body hair, broader hips, larger breasts, weaker bones, lower E, decr muscle mass, strength, may be taller than average
associated RFs/dz: breast CA, thromboembolic dz, osteoporosis
what is turner syndrome? what is special about turner syndrome? presentation?
45X, 46XX, 47XXX sex chromosome aneuploidy only monosomy consistent with life! 50% are 45X presentation: short stature, infertility (ovarian dysgenesis, primary gonadal failure), osteoporosis, cubitus valgus, low posterior hairline, carb intolerance, HTN, short metacarpals, high arched palate, structural abn in KDs, Hashimoto's, neurocognitive problems
what is “alien 3 syndrome?” common misconception? presentation? error where?
47XYY
not overtly violent
tall stature otherwise normal clinical phenotype
nondisjuction occurs during meiosis II - sperm gets extra Y chromosome
what is Fragile X syndrome? why is it called this? what is it due to? severity of dz dt what?
called fragile b/c portion of X chromosome is “dangling by a thread”
due to unstable CGG repeat at Xq27 - expansion of CGG affects fragile X mental retardation gene on X chromosome which results in failure to express a protein required for normal neural development
expansion from pre to full mutation occurs through female meiosis
severity of dz correlates w/# of CGG repeats
how common is fragile X? characteristics?
MC form of mental retardation
most widespread single gene cause of autism
characteristics = broad forehead, elongated face, large prominent ears, strabismus, highly arched palate, hyper extensible joints, hand calluses, pectus excavatum, MVP, enlarged testicles, hypotonia, soft/fleshy skin, flat feet, seizures, hyper extensible finger joints, double jointed thumbs, postpubescent macroorchidism
what is huntington dz dt? chance of having the dz if a parent is affected? ssxs usu appear when? presentation?
neurodegenerative AD dz caused by expansion of CAG triplet repeat stretch w/in huntington gene (37-80 repeats in HD vs 10-26 in healthy genes) - results in mutation protein that damages the brain
any child of an affected parent has 50% chance of getting the dz
usu ssxs begin at 35-44 yo
presentation: chorea, mood and cognitive changes (dementia), gait abn
what are proto-oncogenes? 5 types? functions?
highly regulated proteins involved in control of cell growth
- EC GFs
- GF receptors
- IC signal transducers
- nuclear transcription factors
- tumor suppressor genes
functions: synthesis of receptors, synthesis of messenger system, involved in a nuclear transcription
3 places in the cell that proto-oncogenes become oncogenes?
receptors
messenger systems
nuclear transcription
what can go wrong with receptor synthesis?
amplification: HER2/neu (aka ERB2) leading to BrCA
point mutation: RET –> MEN IIa, IIb
what can go wrong with cells messenger system and what can it result in?
point mutation: RAS –> colon and pancreatic CA, leukemia (GTP signal transduction, receptor function)
translocation: ABL –> 9,22 CML (tyrosine kinase activity, non-receptor fxn)