M2C 1

Front 1

human pol alpha

Back 1

DNA polymerase that associates w/ primase; no proofreading bc template falls off anyway

Front 2

pol delta

Back 2

bulk of DNA synthesis; most associated w/ PCNA clamp; high processivity

Front 3

pol epsilon

Back 3

responsible for genome replication; high processivity; exonulcease activity; not bound to clamp

Front 4

repair mechanism for deamination/depurination?

Back 4

BER

Front 5

repair mechanism for UV photoproducts, adducts, corr-links?

Back 5

NER

Front 6

repair mechanism for replication errors?

Back 6

MMR

Front 7

repair mechanism for ds breaks, adducts, cross-links?

Back 7

HR

Front 8

repair mechanism for ds breaks?

Back 8

EJ

Front 9

three requirements for maintenance in cells

Back 9

1) centromere to mediate segregation during division 2) telomere to protect chromosome ends 3) origins of replication

Front 10

type of histone (variant) in nucleosome contromeres & its function

Back 10

CENP-A; helps direct kinetochore attachment

Front 11

telomere structure

Back 11

500-2000 repeats of GGGTTA

Front 12

what's different about telomere synthesis?

Back 12

doesn't work off a DNA template-- uses RNA strand intrinsic to telomerase

Front 13

by what mechanism is the end of the chromosome protected from degradation?

Back 13

telmeres loop back, insert themselves into double helix; fork stabilized by TRF-II (telomere repeat binding factor II)

Front 14

the histone octamers is _______ly charged and the DNA wraps around it x times

Back 14

positive, twice (70bp/turn for ~145 bp total)

Front 15

diameter of histone solenoid?

Back 15

30 nm

Front 16

penetrance

Back 16

the likelihood that a mutation will have a phenotypic effect

Front 17

variable expressivity

Back 17

range of severity of phenotypic expression amongst people w/ same phenotype

Front 18

pleiotropy

Back 18

diversity of phenotypic effects of same mutations throughout organ systems

Front 19

why is it particularly difficult to diagnose mitochondrial disease?

Back 19

the sample mitochondria most easily obtained are from the serum-- ie lymphocytes, neutrophils-- but these often have not inherited a significant amount of mutant mitochondria

Front 20

three properties of globular proteins

Back 20

1) hydrophobics on the inside, polar on the outside 2) residues on the inside tightly packed, conferring rigidity 3) nearly all buried O2 and N2s have H-bond partners

Front 21

properties of fibrous proteins

Back 21

repetitive sequence; found in tissue that has stress-bearing or motive functions. sequence often Gly-Pro-Hydr (hence scurvy-- prolyl hydroxylase has VitC as a cofactor)

Front 22

properties of integral membrane proteins

Back 22

unlike globular proteins, the exterioir of IMPs are generally hydrophobic

Front 23

stabilizing force in protein-protein interactions?

Back 23

H-bonding (weak enough to prevent aggregation-- more specific)

Front 24

disulfide bonds are more stable in an _____ environment, and therefore more prevalent in _______ (intra/extra) cellular proteins

Back 24

oxidizing, extracellular

Front 25

common post-translational modifications:

Back 25

proteolytic processing (ie insulin), phosphorylation (O2 --> Ser, Thr, Tyr), methylation, hydroxylation, glycoslyation (carboxyl group addition; stabilizes protein interaction w/ membrane)

Front 26

disadvantage of NMR?

Back 26

only works on small proteins

Front 27

recongition subunit of prok. RNA polymerase?

Back 27

sigma

Front 28

how is transcription (roughly) regulated in proks?

Back 28

binding affinity of polymerase to consensus promoter seq & trans-acting elements

Front 29

function of RNA Pol I

Back 29

found in nucleolus; transcribes rRNA genes encoding 45S precursor RNA that gives rise to 28S, 18S, & 5.8S rRNAs.

Front 30

function of RNA Pol II

Back 30

transcribes protein-encoding genes in nucleus and small regulatory RNAs (mi, sn, sno etc)

Front 31

function of RNA Pol III

Back 31

transcribes nuclear transfer RNA genes, 5S rRNA genes, snRNA (required for RNA splicing), 7S RNA for the signal recognition particle, and a few

Front 32

which domain of RNA Pol II is unique and why?

Back 32

C-terminal domain (CTD) of RNA polymerase II is unique and is involved in regulation of the enzyme

Front 33

most genes in eukaryotes are transcribed by _____________

Back 33

RNA Pol II

Front 34

can any of the RNA pols recognize their DNA directly?

Back 34

nope, they all need TFs

Front 35

most important TF for RNAPII?

Back 35

TFIID

Front 36

which TF binds BREs?

Back 36

TFIIB

Front 37

mediators act as a bridge btw ____ and _____

Back 37

enhanced/activator complexes and RNAIIP

Front 38

B (pos) thalassemia is caused by a mutation in a ______ promoter element

Back 38

proximal

Front 39

spinocerebellar ataxia 17 is caused by __________

Back 39

a (trinucleotide repeat expansion) mutation in TATA binding protein

Front 40

two DNA helicase subunits are found in _____________, the last TF to bind during transcription initiation. this TF also phosphorylates the CTD of the RNAPII.

Back 40

TFIIH

Front 41

euk cells rely on ___________ to prevent the polymerase from staling and falling off

Back 41

elongation factors

Front 42

xeroderma pigmentosa is caused by mutations in the ________________- subunits of ___________

Back 42

helicase, THIIH

Front 43

mutations in the transcription elongation factor CS-B cause the disease _____, which results in abnormal and slow growth and development, cutaneous photosensitivity, thin, dry hair, a progeroid (premature aging) appearance, delayed neural development and mental retardation

Back 43

Cockayne's syndrome (CS)

Front 44

which poylmerase indirectly directs the rate of cell growth?

Back 44

RNAPI

Front 45

RNA Pol I promoters? TFs?

Back 45

UCE and Core Elements; Upstream Binding Factor; Pol I transcription activation is very rapid

Front 46

RNAPI elongation & termination?

Back 46

elongation is highly processive; termination is seq-spec

Front 47

Genes transcribed by RNAP III are unusual in that ___________________

Back 47

most have internal promoters, that is, promoters entirely within the transcribed regions of the genes.

Front 48

the critical step required to recruit RNAP III is binding of ______ which contains _____

Back 48

TFIIB, TBP

Front 49

regulatory molecules for Hb (can alter its affinity for O2)?

Back 49

BPG, H+, CO2

Front 50

Myoglobin, cytoglobin, and neuroglobin transport oxygen from cell membrane to _________

Back 50

the mitochondria

Front 51

the secondary structure of Hb and its relatedO2 carries is composed exclusively of ________

Back 51

a-helices

Front 52

neuroglobin remain _________, while hemoglobin forms a _________

Back 52

monomeric, (hetero)tetramer

Front 53

two-log rule

Back 53

if you are at the pK, then it takes one log increase in H+ to almost fully load the binding site, or a one-log decrease in H+ to unload.

Front 54

Binding of protons to Hb causes an important _______ in affinity for O2; this helps Hb unload more oxygen in the presence of high lactic acid, a by-product of anaerobic glycolysis

Back 54

decrease

Front 55

high temp must decrease the affinity of Hb for O2 because fevers require the oxidation of _________

Back 55

carbs

Front 56

most important factor driving protein folding?

Back 56

hydrophobic effect

Front 57

why do proteins denature @ high temp?

Back 57

entropic effect-- nature favors entropy, and more so at higher temps; keep in mind that the unfolded state is more entropically favorable

Front 58

________ is the aa that helps most with folded-state protein flexibility

Back 58

glycine

Front 59

__________ mutations are more likely to be destabilizing than __________ mutations

Back 59

center/interior, surface

Front 60

if you want to re-engineer a protein to make it less likely to aggregate, three good things to try are:

Back 60

a) hide surface cysteines b) hide surface hydrophobics c) change the pI to make it more charged

Front 61

good ways to prevent protein degredation/improve half-life

Back 61

a) remove free cysteines, as these can stabilize misfolded states, b) use the computer c) remove/alter protease recog seqs

Front 62

three good ways to reduce the rate at which proteins are cleared from the body:

Back 62

a) increase their molec weight (takes longer to get thru kidney b) find a way to recycle the ligand it binds to hit its cell-surface receptor c) make it aggregate-- slow-acting (works for insulin)

Front 63

Hsp70 proteins are highly conserved ATPases of relative molecular mass of 70 kDa. their function is:

Back 63

to bind to nascent polypeptide chains and protect them from aggregating on the ribosome and to maintain proteins in an unfolded state so that they can be translocated across membranes.

Front 64

protein misfolding can be infectious because:

Back 64

fibril growth is a nucleation process, and that once a small fibril has formed it will induce other molecules to aggregate

Front 65

__________ aggregregate at each origin during G1 and are subsequently destroyed, thus insuring that replication at each origin is initiated only once per growth cycle

Back 65

licensing factors

Front 66

the sickle cell mutation is:

Back 66

GluB6----->Val

Front 67

____________ has thus far been the most successful drug used to increase the proportion of HbF in sickle-cell patients

Back 67

hydroxyurea

Front 68

70% of all currently known proteins are ________-

Back 68

enzymes

Front 69

zymogen

Back 69

precursor enzyme that must be cleaved by a protease to become its active form

Front 70

coenzyme

Back 70

complex organic cofactor; eg, ATP, NADH, FADH2

Front 71

for ki values, low means ________ binding and high means _________ binding

Back 71

tight, weak

Front 72

for competitive enzyme inhibitors, significant inhibition is define as a reduction in activity of ≥ ____ %.

Back 72

50%

Front 73

UV radiation typically causes damage in the form of ___________ and is repaired via the _________ pathway

Back 73

pyrimidine dimers, NER

Front 74

BER requires specific DNA ________ to recognize and repair damage

Back 74

glycosylases

Front 75

this type of DNA repair is triggered by the detection of "bubbles" in the DNA

Back 75

mismatch repair

Front 76

________ enzymes, in response to binding a physiological effector, have the ability to undergo a conformational change that alters their affinity for the normal substrate, with a change in Km, while Vmax is not significantly changed

Back 76

K-type

Front 77

there are two primary ways to regulate enzymes:

Back 77

1) change the activity of any existing enzyme 2) change the concentration of enzymes

Front 78

________ add a phosphate group; _________ remove one

Back 78

kinase, phosphatase

Front 79

an abundance of cAMP means that _________ will stay active

Back 79

kinases

Front 80

when binding of a substrate to one subunit produces a favorable conformational effect on binding of S to the next subunit, this is a _______ effect. When an activator or inhibitor changes the affinity towards S, this is a ___________ effect.

Back 80

homotropic, heterotropic

Front 81

advantages of EJ over HR as a repair pathway?

Back 81

EJ is a quick and dirty fix that can occur anytime during the cell cycle; HR ONLY occurs during S phase

Front 82

about what fraction of our genomic DNA is composed of retroposons?

Back 82

1/4 (!!!)

Front 83

Diversity in antibodies is primarily derived through ___ recombination

Back 83

V(D)J

Front 84

RAG1/RAG2 are expressed only in developing ____ cells for the purposes of initiating ______, which is helpful in generating antibody diversity

Back 84

B/T V(D)J recomb

Front 85

Mutations in factors required for _____ repair leads to both immunodeficiency (because lymphocytes cannot resolve double strand break intermediates in V(D)J recombination) as well as general cellular sensitivity to other sources of double strand breaks (e.g. ionizing radiation sensitivity, because they cannot efficiently repair other sources of double strand breaks either).

Back 85

EJ

Front 86

array-comparative genome hybridization detects chromosome abnormalities that are (balanced/unbalanced)

Back 86

unbalanced

Front 87

the general incidence of chromosome abnormalities in newborn surveys is ~1:X

Back 87

1:150

Front 88

non-mosaic autosomal trisomies compatible with life (three):

Back 88

Down Syndrome (T 21), Edwards Syndrome (T 18), and Patau Syndrome (T 13)

Front 89

__________ syndrome is associated with an extra copy of the X chromosome in a male (47,XXY).

Back 89

Kleinfelter

Front 90

_______ syndrome is associated with a missing X chromosome in a female (45,X) and is associated with a characteristic phenotype including short stature, cardiovascular defects, impaired sexual development, and infertility.

Back 90

Turner

Front 91

a ______ inversion includes the centromere and a _________ inversion does not include the centromere.

Back 91

pericentric, paracentric

Front 92

Cri du chat syndrome, Wolf-Hirschhorn syndrome, and 1-p syndrome are all caused by chromosomal _______

Back 92

deletions

Front 93

DiGeorge/velocardiofacial syndrome and Williams syndrome are caused by chromosomal ________

Back 93

microdeletions (unequal crossing over following breaks in low-copy repeat seqs)

Front 94

Myeloid cells that harbor the 9;22 translocation known as the “Philadelphia chromosome” show increased proliferation, decreased programmed cell death, and altered interactions with the extracellular matrix ---> a growth advantage that leads to ______

Back 94

chronic myelogenous lukemia

Front 95

The major site of lipid synthesis is in the _____

Back 95

ER

Front 96

No vesicle fusion occurs with the membranes of ____________ or _________; rather, lipids reach these organelles via phospholipid exchange proteins

Back 96

mitochondria, peroxisomes

Front 97

the _____ protein acts a pause button for translation until the newly synthesized protein reaches its target; when the protein hits the ER lumen, this protein detaches and the signal seq is cleaved off

Back 97

SRP

Front 98

Following synthesis on the RER, proteins in the RER membrane or within the lumen of the RER usually pass to the __________ via ______

Back 98

Golgi apparatus, transfer vesicles

Front 99

the Golgi apparatus _____ and ______ the proteins it recieves

Back 99

modifies (primarily thru glycosylation), sorts

Front 100

The synthesis of nuclear membrane proteins occurs on the ____

Back 100

RER

Front 101

Nonmembrane proteins within the nucleus are synthesized on ___________

Back 101

free cytoplasmic ribosomes

Front 102

fibrinogen is the zymogen of _______ (Factor I) and exists in high concentrations in the blood, waiting to be cleaved by thrombin (Factor II)

Back 102

fibrin

Front 103

DNA is typically methylated by _____

Back 103

DNA methyltransferases (DNMTs)

Front 104

_____________ is a phenomenon in which there is differential expression of the alleles of a gene depending on the parent of origin

Back 104

Imprinting

Front 105

syndromes associated with imprinting:

Back 105

Prader-Willi, Angelman, Beckwith-Wiedemann / Silver-Russell

Front 106

___________ consist of repeating disaccharide units arranged in a linear polymer containing 50 to 25,000 disaccharide units; these are highly _________ly charged; they function as cushioning

Back 106

Glycosaminoglycans (GAGs; aka mucopolysaccharides); negatively

Front 107

__________ forms the core of proteoglycan aggregates

Back 107

halyuronic acid

Front 108

___________ form the characteristic "bottle-brush" structure

Back 108

proteoglycans

Front 109

_________ are proteins which contain one or more oligosaccharide complexes covalently attached to the protein through either N-glycosidic linkages to Asn or
O–glycosidic linkages to Ser or Thr.

Back 109

glycoproteins

Front 110

_________ are mostly carbohydrate, with a little protein

Back 110

proteoglycans

Front 111

________ are mostly protein with a little carbohydrate

Back 111

glycoprotein

Front 112

_______ are cellular zipcodes

Back 112

glycoproteins

Front 113

this type of endocytosis provides a mechanism by which a cell can efficiently take up material which is at very low concentrations in the medium surrounding the cell.

Back 113

receptor-mediated endocytosis

Front 114

The uptake of growth factor receptors by RME and their destruction in lysosomes leads to ____ regulation of the receptors from the cell surface. Until new receptors are synthesized and inserted into the plasma membrane, the cell will not be able to bind and respond to the growth factor

Back 114

down

Front 115

statms are:

Back 115

drugs which inhibit HMG-CoA reductase to block endogenous synthesis of cholesterol with the result that cells synthesize more LDL receptors and clear more LDL from the blood

Front 116

spinal muscular atrophy and Retinitis pigmentosa are ________ disorders

Back 116

splicing-associated

Front 117

_______ replaces the Cap Binding Protein during the first round of translation of the mature mRNA. __________ replaces PolyA Binding Protein II.

Back 117

eIF4E , PolyA Binding Protein I