FTM/Miscellaneous Flashcards
Imatinib
Tyrosine kinase inhibitor - effective for leukaemia
Xeroderma Pigmentosum (XP)
AR, LOF mutation in nucleotide excision repair (NER) genes.
UV light can damage DNA causing dimerisation of pyrimidine residues, esp. thymine.
NER path removes these dimers.
Without removal, DNA adducts impede transcription, important in tumour suppressor gene areas ie p53
Increased risk of basal cell carcinoma, squamous cell carcinoma, melanoma
Rb protein
Tumour suppressor, negatively regulates progression from G0 through G1 to S.
Some viruses target Rb function ie HPV, adenovirus est, etc.
Rb binds to E2F - failure of binding implicated in cervical cancer pathogen.
Neurofibromatosis
NF1 gene on chromosome 17 encodes neurofibromin 1. Functions in Ras pathway.
NF1 mutation - NF type 1. (Von recklinghausen)
AD
Cutaneous neurofibromas, lisch nodules, scoliosis, vision, cafe au lait, epilepsy.
Variable expressivity
Required components for purine synthesis
PRPP, Gly, Asp, Gln –> make IMP, which is then converted to ribonucleotides.
GLY specific to purines. (NOT IN PYRIMIDINE SYNTH)
Required components for pyrimidine synthesis
PRPP + orotic acid (From Asp and Gln) make OMP, which is then converted to ribonucleosides.
Duchennes versus Becker Muscular Dystrophies
Allelic heterogeneity. Similar phenotype, both dystrophin mutations, backers less severe.
Duchennes - frameshift
Becker - point mutation.
Heteroplasmy
Mixture of normal and mutant mitochondrial DNA within a cell or individual. Inconsistent expression of the disease among patients.
DNA Pol delta
Eukaryotic, analogous role to prokaryotic enzyme DNA pol III.
Is the primary enzyme for carrying out DNA replication, and proofreading functions with 3’–>5’ exonuclease activity
Orotic Aciduria
Deficiency of UMP synthase. Get macrocytic anemia (can’t make UMP and thus pyrimidine), NOT improved with B12 or folic acid)
Primate
(Prok) facilitates initiation of activity carried out by DNA pol III by creating an RNA primer - DNA pol III can attach and begin adding deoxynucleotides to 3’ end of lagging strand.
DNAPol I
Enzymatic activity identical to DNA pol III AND 5’–> 3’ exonuclease activity to remove RNA primer created by primase.
Telomerase
Reverse transcriptase enzyme with intrinsic RNA template - adds repetitive sequences of DNA (TTAGGG) to the 3’ end of the parent strand of replicating chromosome to avoid shortening
Prokaryotic DNA replication componenets
Uses 1 ORI. 5’–> 3’
Leading strand complementary 3’–> 5’
lagging strand: okazaki, because parent DNA is 5 - 3 but synthesis MUST proceed 5’-3’.
Helicase - unwinds
SSBP’s - prevent DNA from re-annealing. (Dont want H bonds to attract
Gyrase - topo type II - introduces negative supercoils, relaxing positive that form during helicase unwinding
Primase - synth short RNA segment on ssDNA template
DNA Pol III (main prokaryotic polymerase) - adds DNA nucleotides to OH gropu on 3’ end. Also have DNA pol I, II, and II.
Pol I is only polymerase with 5’–>3’ exonuclease activity - decreases RNA primer - lagging strand Synthesis.
Eukaryotic DNA replication components
DNA pol alpha and RNA primase - lay down short series of RNA molecules, pol alpha elongates the RNA primer. Dissociate
Then pol delta takes over: major euk DNA pol. Has 3’–> 5’ exonuclease proofreading activity and does both leading and lagging strand.
