BECOM Exam #3 Flashcards
Helicase
separates the helix by breaking the hydrogen bonds between complementary bases
Single Stranded Binding Protein (SSBP)
prevent reannealing of the duplex during DNA replication
-binds to split single stranded DNA once split by helices so it can not bind back together
Topoisomerase
prevent DNA supercoiling during DNA replication
-doxorubicin poisens
Primase
lays down DNA primer for DNA replication
DNA Pol III
synthesizes daughter strand 5’-3’ direction (continuously on the leading strand, discontinuously on the lagging strand). This results in Okazaki fragments on the lagging strand.
DNA Pol I
replaces the RNA bases of the primer with DNA bases in-between Okazaki fragments
DNA ligase
facilitates the formation of phosphodiester bonds and joins Okazaki fragments
ribonucleoprotein telomerase
synthesized telomeres
telomeres
-are added to the 3’ end of the template strand so there is a over hang and no essential genes are effected
T loop
- the over hating 3’ end loops around and inserts itself into a section of the double stranded telomere
- shelterin protein complexes that specifically bind to telomeric DNA repeats and protects them from being recognized by DNA repair proteins
exonuclease DNA replication
- a section of DNA polymerase
- 3’-OH end of the daughter strand is displaced into exonuclease subunit because of mismatched base pairing
- removes mismatched base pair
- also used to remove primer from Okazaki fragments
PCNA
sliding clamp that makes DNA polymerase more efficient
DNA MYH glycosylase
recognizes and cleaves the damaged DNA bases in DNA excision repair leaving a sugar with no base
AP endonuclease
recognizes sugar with no base during DNA excision repair and cleaves DNA chain
Poly-ADP-ribose polymerase
binds to the strand break and recruits other repair proteins during DNA excision repair
Nonhomologous End Joining
- is used in non dividing cells to repair double stranded breaks in DNA
- single stranded bases are removed by Artemis and the two stands are then put back together by DNA ligase
- Damaged DNA is removed no repaired
Homologous Recombination Repair
- actively dividing cells
- sister is used as a template for repair
- MRN complex binds to end of DNA and activate ATM (Kinase)
- BRCA1, PALB2 and BRCA2 are recruited
HATs
- transfer acetyl group from acetyl-CoA to lysine residues in histone tails
- loosens DNA
HDAC
- removes acetyl group from acetyl-CoA to lysine residues in histone tails
- tightens DNA
DNA Methyltransferase
- associates with the 6’ carbon of cytosine and adds a methyl group to the 5’ carbon
- This favors the incorporation of DNA into heterochromatin (tightly packed, no transcription)
Silencer
- are DNA elements that act at a distance to repress transcription of their target genes
- Silencers bind transcription factors called repressor proteins that induce bends in DNA
Enhancer
- Enhancer sequences increase the level of transcription of specific genes
- They bind proteins that interact with the proteins that are bound to gene promoters, and together the promoters and enhancers drive gene expression
thyroid hormone receptor
- THR bound to RXR (heterodimer)
- Heterodimer bound to corepressor
- Thyroid hormone binds to THR and conformational change binds coactivator
which end is capped and which end get a poly a tail
5’ cap 3’ poly a tail
Initiation
- small ribosomal subunit binds to mRNA strand
- UAC (methionine) bind to to AUG
- large subunit binds and methionine is in the P site
eIF3
prevents premature association of 40S and 60S subunits
eIF2-GTP
- binds to initiator tRNA
- eIF2-GTP/tRNAmet join the 40S ribosomal subunit with participation of eIF3 and other eIFs
- inactive when phosphorylated
- heme dependent
Insulin activates
eIF4
Peptidyl transferase = aminoacyl-tRNA
catalyzes peptide bond formation between amino acids attached to tRNAs at the P and A sites
Using GTP hydrolysis, eEF2
translocates the ribosome, moving it three nucleotides toward the 3’ end of the mRNA
termination
release factors bind to stop codon at the A site he polypeptide bound to the tRNA at the P site is then released while the RF is ejected and the ribosomal subunits separate
Tetracyclines, including doxycycline
prevent the binding of aminoacyl-tRNA by blocking the A (aminoacyl) site of the 30S ribosome
Aminoglycoside antibiotics (Streptomycin, Kanamycin and tobramycin)
have an affinity for the 30S ribosome subunit and don’t allow it to bind with 50s subunit
Erythromycin, roxithromycin, and clarithromycin (macrolides)
- prevent elongation at the transpeptidation step of synthesis by blocking the 50S polypeptide export tunnel.
- binds to the 23S rRNA component of the 50S ribosome and interferes with the assembly of 50S subunits.
Lincomycin and clindamycin
specific inhibitors of peptidyl transferase
B. pseudomallei toxin
targets the translation initiation factor 4A (eIF4A)
Shigella dysenteriaeand enterohemorrhagic strains ofE. coli
remove a specific adenine from 28S ribosomal RNA
Diphtheria toxin
- 0inactivate eukaryotic elongation factor eEF2, thereby inhibiting eukaryotic protein synthesis (prevents translocation)
- DT targets a PTM-modified histidine residue of EF2 called diphthamide, which is only present in eukaryotes and archaea
Mutation in coding region results in
abnormal protein
Regulatory region mutation results in
excessive amount of protein
Translocation results in
novel protein
Gene amplification results in
excessive amount of protein
Stop codons
UAA, UAG, UGA
BAD
proapoptotic
p21
universal cyclin/cdk inhibitor (CKI), it prevents the phosphorylation of Rb, keeping Rb bound to E2F
Rb/E2F
Rb usually sequesters the transcription factor E2F (family of transcription factors)
p53
- stimulate transcription of p21
- cyclin/CDK inhibitor
- activates genes for apoptosis when DNA is not repaired
- activates transcription of DNA repair enzymes
MDM2
- down regulation of p53
- tags p53 for degradation when DNA is successfully repaired
β-catenin
- translocates to the nucleus and activates transcription of myc and cyclin D when not bound to APC
- when bound to APC –> degraded
HOXD13 mutations
causes webbed fingers, too many fingers, or not enough fingers
All axial and appendicular skeletal muscles, and all of the skeleton except the cranium, come from the
paraxial mesoderm
Limb skin, hair, skin glands, and nails
surface ectoderm
Proximodistal axes of development
pectoral/pelvic girdle -> digital tips
Dorsoventral axes of development
- spinal column (back/dorsum) -> belly (front/anterior)
- Important for patterning the extensors dorsally and flexors ventrally
Anteroposterior axes of development
head -> tail (rostral -> caudal)
FGF10
- starts limb bud growth
- FGF8 and FGF10 are important for continuing growth of the arm
Sonic hedgehog (Shh or SHH) is responsible for
Anteroposterior growth axis
apoptosis of hands and feet
loss of webbed fingers and toes
uplimb rotates
dorsally (laterally)
lower limb rotates
- ventrally (medially)
- so souls of feet will be on the ground
- most problem where legs don’t rotate enough
what supplies the arteries of the upper and lower limb through development
primary axial artery
Amelia
Absence of limb(s)
Meromelia
- Absence of parts of limbs
- Can be caused by HOX mutations and teratogens – remember thalidomide
Autosomal Recessive Inheritance
- If both parents have the disorder, all children will have
- The sex ratio of affected offspring is expected to be equal
Autosomal Dominant Inheritance
- Fathers can give to DAUGHTERS and SONS
- Males and females are affected in equal numbers
Autosomal Dominant Inheritance (Sex Limited)
Male-limited precocious puberty, a sex-limited autosomal dominant disorder expressed exclusively in males that affects secondary sex characteristics
Incomplete Penetrance
some individuals will not express the trait even though they carry the allele
X-linked Recessive Inheritance
- A recessive male mated to a homozygous dominant female produces all offspring with the dominant phenotype, and all female offspring are carriers
- Matings of recessive males with carrier females give half dominant and half recessive offspring of both sexes
- Matings of homozygous recessive females with dominant males produce all dominant (carrier) female offspring and all recessive male offspring
X-linked Dominant Inheritance
-Males cant pass X linked trait to son
but all daughters will be effected
Random X-Chromosome Inactivation
one of two X chromosomes in each female somatic cell is randomly inactivated
HOX genes
a subset of homeotic genes, are a group of related genes that control the body plan of an embryo along the head-tail axis
Synpolydactyly mutation cause
HOXD13
Apical epidermal ridge
is a structure that forms from the ectodermal cells at the distal end of each limb bud and acts as a major signaling center to ensure proper development of a lim
what is derived from the paraxial mesoderm
All axial and appendicular skeletal muscles, and all of the skeleton except the cranium
what is derived from the surface ectoderm
Limb skin, hair, skin glands, and nails
Proximodistal
pectoral/pelvic girdle -> digital tips
Dorsoventral
spinal column (back/dorsum) -> belly (front/anterior)
Anteroposterior
head -> tail (rostral -> caudal)
Proximodistal growth axis of limb buds are induced by
FGF10 induction
AER secretes FGF8, FGF4
Zone of Polarizing Activity
- is an area of mesenchyme that contains signals which instruct the developing limb bud to form along the anterior/posterior axis
- located posteriorly
- associated with Sonic hedgehog gene
apoptosis
loss of webbing
Upper limb rotates and movement
- dorsally (laterally)
- Arm buds move cranially so the arm will get closer to the head w growth
Lower limb rotates
ventrally (medially)
Arterial supply to arm buds
primary axillary artery